Evaluating the carotid plaque: going beyond stenosis.

BACKGROUND: Carotid disease is an important cause of ischemic stroke. Traditionally, therapeutic efforts in carotid disease have been aimed at identifying carotid stenosis in symptomatic patients and treating high-grade stenosis. New research suggests that identifying the vulnerable plaque in symptomatic or asymptomatic patients may be a more rational approach for the prevention of ischemic events. METHODS: The author reviews some key references on identification of the vulnerable carotid plaque using different imaging modalities and using biochemical markers. The potential applications of such tools are discussed. RESULTS: Carotid ultrasound, computed tomography, and magnetic resonance angiography can help identify plaque features associated with the so-called vulnerable plaque. Carotid ultrasound is the most widely studied modality and the easiest to perform and interpret. Concomitant measurement of serum biochemical markers associated with atherosclerosis, inflammation, and thrombosis may help identify the vulnerable carotid plaque. CONCLUSIONS: A multimodal approach to studying the carotid plaque appears to be a promising tool in identifying vulnerable carotid plaques. The current literature suggests that in addition to the degree of stenosis other imaging and biochemical findings have important clinical significance.

Early and late recurrence of ischemic lesion on MRI: evidence for a prolonged stroke-prone state?

BACKGROUND: Based on previous observations of a high rate of ischemic lesion recurrence on diffusion-weighted imaging (DWI) within 1 week after an acute ischemic stroke, the authors hypothesized that silent new ischemic lesions are common between 1 week and 90 days after index stroke and that early lesion recurrence may be associated with late lesion recurrence. METHODS: The authors studied 80 acute ischemic stroke patients who had initial MRI performed within 48 hours, and follow-up scans at 5 days and at 30 or 90 days after onset. Early lesion recurrences were defined as new ischemic lesions on 5-day DWI, and late lesion recurrences were defined as those on 30- or 90-day DWI or fluid attenuation inversion recovery image. Early lesion recurrence occurring outside the initial perfusion deficit was termed distant lesion recurrence. RESULTS: Late lesion recurrence occurred in 26%, more frequently observed on 30-day MRI than 90-day MRI (p = 0.016). Early lesion recurrence (OR 4.0; 95% CI 1.3 to 11.7) and distant early lesion recurrence (OR 6.9; 95% CI 1.5 to 32.2) were independently associated with late lesion recurrence by multiple logistic regression analyses. CONCLUSIONS: There may be a continued risk for recurrent ischemic lesions in the weeks following the clinically symptomatic stroke. Future studies are needed to investigate whether MRI-defined ischemic lesion recurrences predict subsequent clinical recurrence and thus may be a potential surrogate endpoint in stroke secondary prevention trials.

Simultaneous bilateral internal carotid and vertebral artery dissection following chiropractic manipulation: case report and review of the literature.

Single-vessel cervical arterial dissections typically occur in young adults and are a common cause of cerebral ischemia and stroke. Although the pathogenesis of multivessel dissection is unclear, it is thought to be a consequence of underlying collagen vascular disease. We present a 34-year-old previously healthy man who developed bilateral internal carotid and vertebral artery dissection following chiropractic manipulation.

Continuous arterial spin labeling perfusion magnetic resonance imaging findings in postpartum vasculopathy.

Postpartum vasculopathy (PPV) is a rare heterogeneous nonatherosclerotic vasculopathy that occurs in the puerperium. It occurs spontaneously but may be triggered by vasoconstrictor substances. The angiographic findings vary and include narrowing of the intracranial arteries and vasospasm. The angiographic findings and the occurrence of ischemic infarcts suggest that cerebral blood flow (CBF) is impaired in PPV. The purpose of this study is to determine CBF in patients with PPV. The authors conducted a case study of 3 patients with clinical and laboratory criteria for PPV examined during a 2-year period. Clinical examination, computed tomography imaging, structural magnetic resonance imaging (MRI), cerebral angiography, and continuous arterial spin labeling perfusion (CASL-PI) MRI were performed in all patients. Mean global CBF was determined, and perfusion maps were visually inspected. The CBF values and perfusion maps were correlated with the clinical symptoms and the neuroimaging findings. Three women were studied (22, 34, and 36 years old). The median time of presentation was 4 days postpartum. One presented with intracranial hemorrhage and diffuse arterial narrowing, the other 2 with stroke-like lesions, encephalopathy, and segmental narrowing mainly in the posterior circulation. CASL-PI was performed within 1 week of symptom onset in all 3 patients. Global mean CBF values were 51.8, 39.3, and 41.8 cc/100 g/min. Although global CBF was mildly diminished, it was above ischemic levels. Visual inspection of the CASL-PI perfusion maps did not reveal areas of focal hypoperfusion or hyperperfusion. In this series of patients with PPV, CBF was close to normal. Although angiography often reveals diffuse arterial narrowing, the CBF values encountered in this study do not support a state of generalized or focal oligoemia. Vasomotor tone may change intermittently in patients with PPV.

Predictors of fatal brain edema in massive hemispheric ischemic stroke.

BACKGROUND AND PURPOSE: Early identification of stroke patients at risk for fatal brain edema may be useful in selecting patients for aggressive interventions. Prior studies suggested that early nausea/vomiting and major hypodensity on baseline computed tomography (CT) were predictive of herniation. METHODS: This study was a retrospective multicenter case-control study of patients with large middle cerebral artery (MCA) strokes admitted within 48 hours of symptom onset. Medical records, laboratory data, and CT scans were analyzed. Cases, defined as patients who died of massive brain swelling, were compared with all remaining patients as controls. RESULTS: Two hundred one patients with large MCA strokes were identified: 94 (47%) died of brain swelling, 12 (6%) died of non-neurological causes, and 95 (47%) survived at day 30. Multivariable analysis, adjusted for age and clustered by center, identified the following predictors of fatal brain edema: history of hypertension (OR 3.0, 95% CI 1.2 to 7.6, P=0.02), history of heart failure (OR 2.1, 95% CI 1.5 to 3.0, P<0.001), elevated white blood cell count (OR 1.08 per 1000 white blood cells/microL, 95% CI 1.01 to 1.14, P=0.02), >50% MCA hypodensity (OR 6.3, 95% CI 3.5 to 11.6, P<0.001), and involvement of additional vascular territories (anterior cerebral artery, posterior cerebral artery, or anterior choroidal artery; OR 3.3, 95% CI 1.2 to 9.4, P=0.02). Initial level of consciousness, National Institutes of Health Stroke Scale score, early nausea/vomiting, and serum glucose were associated with neurological death in bivariable but not multivariable analyses. CONCLUSIONS: Among patients with large MCA infarctions, an increased risk of fatal brain edema is associated with history of hypertension or heart failure, increased baseline white blood cell count, major early CT hypodensity involving >50% of the MCA territory, and involvement of additional vascular territories. These data confirm and expand on prior research with a broad-based patient population. The presence of these risk factors identifies those stroke patients who may require aggressive therapeutic approaches.

Aphemia: an isolated disorder of articulation.

Aphemia is a disorder with prominent speech abnormality. Since its description by Broca, there has been debate regarding the neuropsychological disorganization underlying aphemia: is aphemia an articulatory disorder or a language disorder? We describe a patient with markedly impaired articulation, but preserved receptive and written language function and buccal-facial coordination. The location of his stroke was in the left precentral gyrus, undercutting a small area of motor and premotor cortex. This case suggests that aphemia can occur as an isolated articulation deficit without language involvement or more widespread bulbar apraxia, and may be a severe form of apraxia of speech.

Safety of intra-arterial thrombolysis in the postoperative period.

BACKGROUND AND PURPOSE: Limited systemic fibrinolysis and reduced dosage are features of intra-arterial thrombolyis (IAT) that may be advantageous in the treatment of postoperative strokes. However, IAT may increase the risk of surgical bleeding. We sought to determine the safety of postoperative IAT. METHODS: This was a retrospective case series from 6 university hospitals. All cases of IAT within 2 weeks of surgery were identified. Demographics, stroke mechanism, stroke severity, imaging and angiographic findings, time between surgery and lysis, thrombolytic agent used, surgical site bleeding, intracranial bleeding, and mortality rates were determined. Death or complications directly related to IAT were determined. RESULTS: Thirty-six patients (median age, 71.5 years; range, 45 to 85) were identified. Median time from surgery to stroke was 21.5 hours (range, 1 to 120). Open heart surgery was done in 18 (50%), carotid endarterectomy in 6 (17%), craniotomy in 3 (8%), ophthalmologic-ear, nose and throat surgery in 2 (6%), urologic-gynecologic surgery in 4 (11%), orthopedic surgery in 2 (6%), and plastic surgery in 1 (3%). The stroke causes were cardioembolism in 24 (67%), large-vessel atherosclerosis in 4 (11%), dissection in 3 (8%), postendarterectomy occlusion in 4 (11%), and radiation arteriopathy in 1 (3%). Median time to angiogram was 2.5 hours (0.1 to 5.5). Occlusion sites were M1 in 19 (53%), M2 in 9 (25%), internal carotid artery in 5 (14%), basilar artery in 2 (6%), and posterior communicating artery in 1 (3%). Thrombolysis was completed at a median of 4.5 hours (range, 1 to 8.0). Tissue plasminogen activator was used in 19 (53%) and urokinase in 17 (47%). Nine (26%) patients died. Surgical site bleeding occurred in 9 (25%) cases (minor in 6, major in 3). The major surgical bleeds were 2 post-craniotomy intracranial hemorrhages and 1 hemopericardium after coronary artery bypass grafting; all were fatal. Six deaths were non-IAT related: 3 caused by cerebral edema and 3 by systemic causes. Major bleeding complications were significantly more common among patients with craniotomy (P<0.02). CONCLUSIONS: Postoperative IAT carries a risk of bleeding in up to 25% of patients but is usually minor surgical site bleeding. Avoiding IAT in intracranial surgery patients may reduce complications. Mortality rate in this series was similar to that reported in prior IAT trials. IAT remains a viable therapeutic option for postoperative strokes.

Automated CT segmentation and analysis for acute middle cerebral artery stroke.

BACKGROUND AND PURPOSE: The quantitative nature of CT should make it amenable to semiautomated analysis using modern neuroimaging methods. The purpose of this study was to begin to develop automated methods of analysis of CT scans to identify putative hypodensity within the lentiform nucleus and insula in patients with acute middle cerebral artery stroke. METHODS: Thirty-five CT scans were retrospectively selected from our CT archive (scans of 20 normal control participants and 15 patients presenting with acute middle cerebral artery stroke symptoms). The DICOM data for each participant were interpolated to a single volume, scalp stripped, normalized to a standard atlas, and segmented into anatomic regions. Voxel densities in the lentiform nucleus and insula were compared with the contralateral side at P <.01 using the Wilcoxon two-sample rank sum statistic, corrected for spatial autocorrelation. RESULTS: The quality of the registration for the anatomic regions was excellent. The control group had two false-positive results. The patient group had two false-negative results in the lentiform nucleus, two false-negative results in the insular cortex, and one false-positive finding for the insular cortex. The remainder of the infarcts were correctly identified. The original clinical reading, performed at the time of presentation, produced five false-negative interpretations for the patient group, all of which were correctly identified by the automated algorithm. CONCLUSION: We present an automated method for identifying potential areas of acute ischemia on CT scans. This approach can be extended to other brain regions and vascular territories and may aid in the interpretation of CT scans in cases of hyperacute stroke.

MRI identification of early white matter injury in anoxic-ischemic encephalopathy.

BACKGROUND: Anoxic-ischemic encephalopathy (AIE) affects the gray matter more than the white matter. Recent animal experiments suggest that the white matter is more sensitive to ischemia than previously thought. The authors describe the MRI findings in seven patients with AIE who demonstrate early preferential involvement of the white matter. MATERIALS AND METHODS: A retrospective case series study was performed, including seven patients with AIE who underwent MRI of the brain within 7 days of insult. Demographic information, type of insult, clinical examination findings, EEG findings, and clinical outcome were obtained. MRI studies were reviewed with specific attention to the cortex, deep gray matter, and the white matter structures. Mean apparent diffusion coefficient (ADC) was calculated in regions of interest placed in the cerebellar hemispheres, putamen, thalamus, splenium of corpus callosum, centrum semiovale, and medial frontal cortex. RESULTS: The causes of AIE were cardiac arrhythmias in two patients, myocardial infarction in one, drug overdose in two, carbon monoxide poisoning in one, and respiratory failure and sepsis in one. The median time to MRI was 2.5 days. Symmetric areas of restricted diffusion were found in the periventricular white matter tracts (7/7 patients), the corpus callosum (6/7 patients), internal capsule (5/7 patients), and the subcortical association fibers (3/7 patients). ADC maps confirmed the restricted diffusion. Gray matter involvement was seen in three patients, and was more prominent on conventional imaging sequences compared with diffusion-weighted imaging. A subtle decrease in mean ADC was seen in cortex. CONCLUSIONS: Prominent, symmetric restricted diffusion can occur early after AIE in white matter, whereas gray matter involvement may be less prominent. Further studies involving a larger sample and serial imaging are required to confirm these preliminary findings.

Pearls and pitfalls in the intensive care management of Guillain-Barré syndrome.

Approximately one third of patients with Guillain-Barré syndrome (GBS) need to be admitted to the intensive care unit (ICU) because of respiratory failure. A significant proportion of patients require ICU admission because of dysautonomia or because of medical or iatrogenic complications. Recognition of the clinical manifestations and the paraclinical findings in patients with neuromuscular respiratory failure is essential to ensure mechanical ventilation promptly. In the ICU, attention to positioning, nutrition, analgesia, and psychological support are crucial. Recognition of autonomic dysfunction and of the rare need for intervention is important to avoid iatrogenic complications. Prognosis determination in GBS is based on the clinical history, epidemiological factors, and neurologic examination.

Treatment of Bickerstaff's brainstem encephalitis with immune globulin.

Bickerstaff's brainstem encephalitis (BBE) is an immune disorder of unknown etiology. Previous reports of successful treatment of BBE involved steroids or plasma exchange. We describe a patient with BBE who demonstrated rapid clinical recovery after treatment with intravenous immune globulin. Our findings suggest that IVIg is an alternative treatment in BBE, especially when plasma exchange is difficult or contraindicated. Our patient also demonstrated pseudoretraction and pseudoptosis during clinical recovery, an observation which supports a differential immune attack on components of the third nerve or supranuclear regions, and expands our understanding of the pathophysiology of BBE.

Magnetic resonance perfusion imaging in acute ischemic stroke using continuous arterial spin labeling.

BACKGROUND AND PURPOSE: Continuous arterial spin-labeled perfusion MRI (CASL-PI) uses electromagnetically labeled arterial blood water as a diffusible tracer to noninvasively measure cerebral blood flow (CBF). We hypothesized that CASL-PI could detect perfusion deficits and perfusion/diffusion mismatches and predict outcome in acute ischemic stroke. METHODS: We studied 15 patients with acute ischemic stroke within 24 hours of symptom onset. With the use of a 6-minute imaging protocol, CASL-PI was measured at 1.5 T in 8-mm contiguous supratentorial slices with a 3.75-mm in-plane resolution. Diffusion-weighted images were also obtained. Visual inspection for perfusion deficits, perfusion/diffusion mismatches, and effects of delayed arterial transit was performed. CBF in predetermined vascular territories was quantified by transformation into Talairach space. Regional CBF values were correlated with National Institutes of Health Stroke Scale (NIHSS) score on admission and Rankin Scale (RS) score at 30 days. RESULTS: Interpretable CASL-PI images were obtained in all patients. Perfusion deficits were consistent with symptoms and/or diffusion-weighted imaging abnormalities. Eleven patients had hypoperfusion, 3 had normal perfusion, and 1 had relative hyperperfusion. Perfusion/diffusion mismatches were present in 8 patients. Delayed arterial transit effect was present in 7 patients; serial imaging in 2 of them showed that the delayed arterial transit area did not succumb to infarction. CBF in the affected hemisphere correlated with NIHSS and RS scores (P=0.037 and P=0.003, Spearman rank correlation). The interhemispheric percent difference in middle cerebral artery CBF correlated with NIHSS and RS scores (P=0.007 and P=0.0002, respectively). CONCLUSIONS: CASL-PI provides rapid noninvasive multislice imaging in acute ischemic stroke. It depicts perfusion deficits and perfusion/diffusion mismatches and quantifies regional CBF. CASL-PI CBF asymmetries correlate with severity and outcome. Delayed arterial transit effects may indicate collateral flow.

Safety of air medical transportation after tissue plasminogen activator administration in acute ischemic stroke.

BACKGROUND AND PURPOSE: We sought to determine the safety of air medical transport (AMT) of patients with acute ischemic stroke (AIS) immediately after or during administration of tissue plasminogen activator (tPA). Patients with AIS treated with tPA in nonuniversity hospitals frequently need transfer to tertiary care centers that can provide specialized care. AMT is a widely available mode of transport that is crucial in providing expedient and quality health care to critically ill patients while assuring high level of care during transportation. The safety of AMT of patients with AIS after or during administration of tPA has not been examined. METHODS: We performed retrospective chart review of 24 patients with AIS who were treated with intravenous tPA and transferred by helicopter to the Hospital of the University of Pennsylvania or the University of Cincinnati Hospital. The charts were reviewed for neurological complications, systemic complications, and adherence to the National Institutes of Neurological Disorders and Stroke (NINDS) protocol for AIS management. RESULTS: No major neurological or systemic complications occurred. Four patients had hypertension warranting treatment, 3 patients experienced motion sickness, 1 patient developed a transient confusional state, and 1 patient experienced minor systemic bleeding. Four NINDS protocol violations occurred, all related to blood pressure management. CONCLUSIONS: In this small series, AMT of AIS patients after thrombolysis was not associated with any major neurological or systemic complications. Flight crew education on the NINDS AIS protocol is essential in limiting the number of protocol violations. AMT of patients with AIS provides fast and safe access to tertiary centers that can provide state of the art stroke therapy.

Reliability and validity of estimating the NIH stroke scale score from medical records.

BACKGROUND AND PURPOSE: The aim of our study was to determine whether the National Institutes of Health Stroke Scale (NIHSS) can be estimated retrospectively from medical records. The NIHSS is a quantitative measure of stroke-related neurological deficit with established reliability and validity for use in prospective clinical research. Recently, retrospective observational studies have estimated NIHSS scores from medical records for quantitative outcome analysis. The reliability and validity of estimation based on chart review has not been determined. METHODS: Thirty-nine patients were selected because their NIHSS scores were formally measured at admission and discharge. Handwritten notes from medical records were abstracted and NIHSS scores were estimated by 6 raters who were blinded to the actual scores. Estimated scores were compared among raters and with the actual measured scores. RESULTS: Interrater reliability was excellent, with an intraclass correlation coefficient of 0.82. Scores were well calibrated among the 6 raters. Estimated NIHSS scores closely approximated the actual scores, with a probability of 0.86 of correctly ranking a set of patients according to 5-point interval categories (as determined by the area under the receiver-operator characteristic curve). Patients with excellent outcomes (NIHSS score of