Multi-Center Study of Diffusion-Weighted Imaging in Coma After Cardiac Arrest.

BACKGROUND: The ability to predict outcomes in acutely comatose cardiac arrest survivors is limited. Brain diffusion-weighted magnetic resonance imaging (DWI MRI) has been shown in initial studies to be a simple and effective prognostic tool. This study aimed to determine the predictive value of previously defined DWI MRI thresholds in a multi-center cohort. METHODS: DWI MRIs of comatose post-cardiac arrest patients were analyzed in this multi-center retrospective observational study. Poor outcome was defined as failure to regain consciousness within 14 days and/or death during the hospitalization. The apparent diffusion coefficient (ADC) value of each brain voxel was determined. ADC thresholds and brain volumes below each threshold were analyzed for their correlation with outcome. RESULTS: 125 patients were included in the analysis. 33 patients (26%) had a good outcome. An ADC value of less than 650 × 10(-6) mm(2)/s in ≥10% of brain volume was highly specific [91% (95% CI 75-98)] and had a good sensitivity [72% (95% CI 61-80)] for predicting poor outcome. This threshold remained an independent predictor of poor outcome in multivariable analysis (p = 0.002). An ADC value of less than 650 × 10(-6) mm(2)/s in >22% of brain volume was needed to achieve 100% specificity for poor outcome. CONCLUSIONS: In patients who remain comatose after cardiac arrest, quantitative DWI MRI findings correlate with early recovery of consciousness. A DWI MRI threshold of 650 × 10(-6) mm(2)/s in ≥10% of brain volume can differentiate patients with good versus poor outcome, though in this patient population the threshold was not 100% specific for poor outcome.

Prognostication of neurologic outcome in cardiac arrest patients after mild therapeutic hypothermia: a meta-analysis of the current literature.

PURPOSE: To assess the sensitivity and false positive rate (FPR) of neurological examination and somatosensory evoked potentials (SSEPs) to predict poor outcome in adult patients treated with therapeutic hypothermia after cardiopulmonary resuscitation (CPR). METHODS: MEDLINE and EMBASE were searched for cohort studies describing the association of clinical neurological examination or SSEPs after return of spontaneous circulation with neurological outcome. Poor outcome was defined as severe disability, vegetative state and death. Sensitivity and FPR were determined. RESULTS: A total of 1,153 patients from ten studies were included. The FPR of a bilaterally absent cortical N20 response of the SSEP could be calculated from nine studies including 492 patients. The SSEP had an FPR of 0.007 (confidence interval, CI, 0.001-0.047) to predict poor outcome. The Glasgow coma score (GCS) motor response was assessed in 811 patients from nine studies. A GCS motor score of 1-2 at 72 h had a high FPR of 0.21 (CI 0.08-0.43). Corneal reflex and pupillary reactivity at 72 h after the arrest were available in 429 and 566 patients, respectively. Bilaterally absent corneal reflexes had an FPR of 0.02 (CI 0.002-0.13). Bilaterally absent pupillary reflexes had an FPR of 0.004 (CI 0.001-0.03). CONCLUSIONS: At 72 h after the arrest the motor response to painful stimuli and the corneal reflexes are not a reliable tool for the early prediction of poor outcome in patients treated with hypothermia. The reliability of the pupillary response to light and the SSEP is comparable to that in patients not treated with hypothermia.

Predicting outcome after acute basilar artery occlusion based on admission characteristics.

OBJECTIVE: To develop a simple prognostic model to predict outcome at 1 month after acute basilar artery occlusion (BAO) with readily available predictors. METHODS: The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational, international registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO. We considered predictors available at hospital admission in multivariable logistic regression models to predict poor outcome (modified Rankin Scale [mRS] score 4-5 or death) at 1 month. We used receiver operator characteristic curves to assess the discriminatory performance of the models. RESULTS: Of the 619 patients, 429 (69%) had a poor outcome at 1 month: 74 (12%) had a mRS score of 4, 115 (19%) had a mRS score of 5, and 240 (39%) had died. The main predictors of poor outcome were older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIH Stroke Scale (NIHSS) score, and longer time to treatment. A prognostic model that combined demographic data and stroke risk factors had an area under the receiver operating characteristic curve (AUC) of 0.64. This performance improved by including findings from the neurologic examination (AUC 0.79) and CT imaging (AUC 0.80). A risk chart showed predictions of poor outcome at 1 month varying from 25 to 96%. CONCLUSION: Poor outcome after BAO can be reliably predicted by a simple model that includes older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIHSS score, and longer time to treatment.

Clinical assessment of standard and generalized autocalibrating partially parallel acquisition diffusion imaging: effects of reduction factor and spatial resolution.

BACKGROUND AND PURPOSE: PI improves routine EPI-based DWI by enabling higher spatial resolution and reducing geometric distortion, though it remains unclear which of these is most important. We evaluated the relative contribution of these factors and assessed their ability to increase lesion conspicuity and diagnostic confidence by using a GRAPPA technique. MATERIALS AND METHODS: Four separate DWI scans were obtained at 1.5T in 48 patients with independent variation of in-plane spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1 versus R = 3). A neuroradiologist with access to clinical history and additional imaging sequences provided a reference standard diagnosis for each case. Three blinded neuroradiologists assessed scans for abnormalities and also evaluated multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic regression was used to determine the impact of each factor on subjective image quality and confidence. RESULTS: Reference standard diagnoses in the patient cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n = 5). While readers preferred both a higher reduction factor and a higher spatial resolution, the largest effect was due to an increased reduction factor (odds ratio, 47 ± 16). Small lesions were more confidently discriminated from artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward the reference standard reading and exclusively for posterior fossa lesions. CONCLUSIONS: PI improves DWI primarily by reducing geometric distortion rather than by increasing spatial resolution. This outcome leads to a more accurate and confident diagnosis of small lesions.

The neurocritical care research network: NCRN.

Neurocritical care diseases carry a high morbidity and mortality. Therapeutic and technological advances in neurocritical care have greatly improved the outcome of a variety of life-threatening disorders including traumatic brain injury, acute ischemic stroke, intracerebral and subarachnoid hemorrhage, and anoxic injury following cardiac arrest. These advances have stemmed from a better understanding of the physiology of neurocritical care illnesses, improved neuromonitoring techniques, and the introduction of more efficacious treatments. Despite all the advances in neuromonitoring, diagnostic imaging, and emerging treatments, much research needs to be undertaken in neurocritical care. Many of the clinical trials carried out in the general critical care population have excluded neurocritical care patients. For instance, the landmark ARDSNET trial that demonstrated the beneficial effects of low tidal volume ventilation in patients with ARDS cannot be directly applied to neurocritical care patients who frequently may experience this pulmonary complication. There is a need for a more cohesive and integrated research system or network to establish a track record for high-quality, investigator-initiated clinical research in neurocritical care. Such a system may help us overcome potential impediments to the future advancement of neurocritical care research. We propose the creation of the neurocritical care research network. The mission of the Network is to facilitate multicenter and multidisciplinary collaboration and patient enrollment in clinical trials of specific neurocritical care diseases.

Research priorities in neurocritical care.

This summary of the last session of the First Neurocritical Care Research Conference reviews the discussions about research priorities in neurocritical care. The first presentation reviewed current projects funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and potential models to follow including an independent Neurocritical Care Network or the creation of such a network with the goal of collaborating with already existing ones. Experienced neurointensivists then presented their views on the most common and important research questions that need to be answered and investigated in the field. Finally, utility of clinical registries was discussed emphasizing their importance as hypothesis generators. During the group discussion, interests in comparative effectiveness research, the use of physiological endpoints from monitoring and alternate trial design were expressed.

Clinical trial design in the neurocritical care unit.

Clinical trials provide a robust mechanism to advance science and change clinical practice across the widest possible spectrum. Fundamental in the Neurocritical Care Society's mission is to promote Quality Patient Care by identifying and implementing best medical practices for acute neurological disorders that are consistent with the current scientific knowledge. The next logical step will be to foster rapid growth of our scientific body of evidence, to establish and disseminate these best practices. In this manuscript, five invited experts were impaneled to address questions, identified by the conference organizing committee as fundamental issues for the design of clinical trials in the neurological intensive care unit setting.

The critical care research networks experience.

Neurocritical care is a subspecialty of critical care medicine, dedicated to the care and the advancement of care of critically ill patients with neurosurgical or neurological diseases. Neurocritical care patients are heterogeneous, in both their disease process and the therapies they receive, however, several studies demonstrate that care of these patients in dedicated NeuroIntensive Care Units (neuroICUs) by neurointensivists, who coordinate their care is associated with reduced mortality and resource utilization. NeuroICUs foster innovation, and yet despite all the recent advances, much research needs to be undertaken in neurocritical care to better understand the disease pathophysiology and to demonstrate improved outcome with the use of goal-directed therapy based on evolving techniques and therapies.

Research and technology in neurocritical care.

The daily practice of neurointensivists focuses on the recognition of subtle changes in the neurological examination, interactions between the brain and systemic derangements, and brain physiology. Common alterations such as fever, hyperglycemia, and hypotension have different consequences in patients with brain insults compared with patients of general medical illness. Various technologies have become available or are currently being developed. The session on "research and technology" of the first neurocritical care research conference held in Houston in September of 2009 was devoted to the discussion of the current status, and the research role of state-of-the art technologies in neurocritical patients including multi-modality neuromonitoring, biomarkers, neuroimaging, and "omics" research (proteomix, genomics, and metabolomics). We have summarized the topics discussed in this session. We have provided a brief overview of the current status of these technologies, and put forward recommendations for future research applications in the field of neurocritical care.

MRI guides diagnostic approach for ischaemic stroke.

BACKGROUND AND AIM: Identification of ischaemic stroke subtype currently relies on clinical evaluation supported by various diagnostic studies. The authors sought to determine whether specific diffusion-weighted MRI (DWI) patterns could reliably guide the subsequent work-up for patients presenting with acute ischaemic stroke symptoms. METHODS: 273 consecutive patients with acute ischaemic stroke symptoms were enrolled in this prospective, observational, single-centre NIH-sponsored study. Electrocardiogram, non-contrast head CT, brain MRI, head and neck magnetic resonance angiography (MRA) and transoesophageal echocardiography were performed in this prespecified order. Stroke neurologists determined TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification on admission and on discharge. Initial TOAST stroke subtypes were compared with the final TOAST subtype. If the final subtype differed from the initial assessment, the diagnostic test deemed the principal determinant of change was recorded. These principal determinants of change were compared between a CT-based and an MRI-based classification schema. RESULTS: Among patients with a thromboembolic DWI pattern, transoesophageal echocardiography was the principal determinant of diagnostic change in 8.8% versus 0% for the small vessel group and 1.7% for the other group (p<0.01). Among patients with the combination of a thromboembolic pattern on MRI and a negative cervical MRA, transoesophageal echocardiography led to a change in diagnosis in 12.1%. There was no significant difference between groups using a CT-based scheme. CONCLUSIONS: DWI patterns appear to predict stroke aetiologies better than conventional methods. The study data suggest an MRI-based diagnostic algorithm that can potentially obviate the need for echocardiography in one-third of stroke patients and may limit the number of secondary extracranial vascular imaging studies to approximately 10%.

Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists.

OBJECTIVE: Physician prediction of outcome in critically ill neurologic patients impacts treatment decisions and goals of care. In this observational study, we prospectively compared predictions by neurointensivists to patient outcomes at 6 months. METHODS: Consecutive neurologic patients requiring mechanical ventilation for 72 hours or more were enrolled. The attending neurointensivist was asked to predict 6-month 1) functional outcome (modified Rankin scale [mRS]), 2) quality of life (QOL), and 3) whether supportive care should be withdrawn. Six-month functional outcome was determined by telephone interviews and dichotomized to good (mRS 0-3) and poor outcome (mRS 4-6). RESULTS: Of 187 eligible patients, 144 were enrolled. Neurointensivists correctly predicted 6-month functional outcome in 80% (95% confidence interval [CI], 72%-86%) of patients. Accuracy for a predicted good outcome was 63% (95% CI, 50%-74%) and for poor outcome 94% (95% CI, 85%-98%). Excluding patients who had life support withdrawn, accuracy for good outcome was 73% (95% CI, 60%-84%) and for poor outcome 87% (95% CI, 74%-94%). Accuracy for exact agreement between neurointensivists' mRS predictions and actual 6-month mRS was only 43% (95% CI, 35%-52%). Predicted accuracy for QOL was 58% (95% CI, 39%-74%) for good/excellent and 67% (95% CI, 46%-83%) for poor/fair. Of 27 patients for whom withdrawal of care was recommended, 1 patient survived in a vegetative state. CONCLUSIONS: Prediction of long-term functional outcomes in critically ill neurologic patients is challenging. Our neurointensivists were more accurate in predicting poor outcome than good outcome in patients requiring mechanical ventilation >or=72 hours.

[Hypertensive encephalopathy: does not only occur at high blood pressure]. / Hypertensieve encefalopathie: niet alleen bij zeer hoge bloeddrukwaarden.

A 45-year-old man presented with severe hypertension, headache, cortical blindness, and a depressed level of consciousness. A second patient, a 33-year-old woman, was admitted with pre-eclampsia. She developed lethargy, headache, bilateral extensor plantar responses, and seizures. The third patient, a 62-year-old man, presented with acute renal failure due to necrotising vasculitis and glomerulonephritis. Five days after treatment with immunosuppressive drugs had been initiated, he developed headache, confusion, seizures, and cortical blindness. Hypertensive encephalopathy is characterised by headache, vomiting, disturbances in cognition and level of consciousness, visual abnormalities, and seizures. Imaging studies often demonstrate oedema of the white matter in the posterior parietal and occipital areas of the brain. This so-called reversible posterior leucoencephalopathy syndrome is well known in patients with severe hypertension, but it is also associated with immunosuppressive drug use and renal failure. It can be recognised by its fairly characteristic clinical features (different combinations of headache, vomiting, changes in cognition and level of consciousness, seizures, muscle weakness, and visual symptoms) and by its specific imaging findings. Treatment consists of reducing the blood pressure and reducing or discontinuing the use of immunosuppressive drugs. If the treatment is started promptly, symptoms and imaging abnormalities are usually reversible.

Retinal ischemia and embolism. Etiologies and outcomes based on a prospective study.

OBJECTIVES: To identify the most likely mechanisms of retinal ischemia and embolism in a hospital-referred population, and to determine the frequency of recurrent vascular events during the 3-month period following initial presentation. METHODS: Consecutive patients presenting to 2 tertiary medical centers and their outpatient clinics were prospectively enrolled over a 22-month period. Eligible patients presented with histories of transient or permanent monocular visual loss, or had evidence of asymptomatic retinal embolism on routine ophthalmological examination. They underwent a rapid and standardized evaluation that included imaging studies as well as blood tests, and follow-up was obtained at 1 and 3 months. RESULTS: Seventy-seven patients were enrolled. Enrollment diagnoses consisted of amaurosis fugax (n = 32), asymptomatic retinal embolism (n = 34), and central or branch retinal artery occlusion (n = 11). Eight different presumed etiologies of retinal artery distribution embolism or hypoperfusion were identified. Extracranial internal carotid artery occlusion or more than 50% stenosis was observed in 17/77 (22.1%) cases, making it the largest etiologic subgroup. Uncommon but treatable conditions were identified in 8/77 (10.4%) patients, and an etiologic diagnosis could not be made in 35/77 (45.5%) patients. Recurrent events occurred in, respectively, 14/77 (18.2%) and 6/73 (8.2%) patients at the 1- and 3-month follow-ups. They included 2 infarcts and 2 deaths; ischemic events of the retina were more common than those involving the brain. CONCLUSION: Severe stenosis of the extracranial internal carotid artery is the most common identified condition associated with retinal ischemia and embolism, but a variety of other, potentially treatable, conditions can be diagnosed if appropriate and specific evaluations are conducted. The frequency of recurrent vascular ischemic events is highest during the 1st month of follow-up and decreases during the 2nd and 3rd months. Recurrences range from relatively innocuous episodes of amaurosis fugax to vascular death.

Diagnostic impact of early transcranial Doppler ultrasonography on the TOAST classification subtype in acute cerebral ischemia.

OBJECTIVE: The impact of early transcranial Doppler ultrasonography (TCD) upon stroke subtype diagnosis is unknown and may affect therapeutic strategies. In this study, the diagnostic usefulness of TCD in stroke subtype diagnosis according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) study was investigated in patients with acute cerebral ischemia. METHODS: TCD examination within 24 h of symptom onset was performed in 50 consecutive patients with acute cerebral ischemia. Of these 54% were female. Sixty percent of patients were black, 36% white, and 4% Asian. Initial TOAST stroke subtype diagnosis (ITSSD) was based upon clinical presentation and initial brain imaging studies. Modified TOAST stroke subtype diagnosis was determined subsequently after additional review of the TCD examination. Final TOAST stroke subtype diagnosis was determined at hospital discharge, incorporating all diagnostic studies. Using final TOAST stroke subtype diagnosis as the 'gold standard' ITSSD and modified TOAST stroke subtype diagnosis were compared in order to determine additional benefit from the information obtained by TCD. Data were collected retrospectively by a single investigator. RESULTS: ITSSD classified 23 of 50 (46%) patients correctly. After TCD, 30 of 50 (60%) patients were classified correctly, for an absolute benefit of 14% and a relative benefit of 30% (p = 0.018). Most benefit from TCD was observed in the TOAST stroke subtype category large-artery atherosclerosis, in particular in patients with intracranial vascular disease. In this category, ITSSD had a sensitivity of 27% which increased to 64% after TCD (p = 0.002). CONCLUSION: TCD within 24 h of symptom onset improves the accuracy of early stroke subtype diagnosis in patients with acute cerebral ischemia due to large-artery atherosclerosis. This may have clinical implications for early therapeutic interventions.

Ophthalmic artery microembolism in giant cell arteritis.

A 70-year-old man presented with a history of headache and sudden loss of vision of the left eye. Funduscopic examination showed sector retinal edema and hemorrhage as well as optic disc swelling consistent with anterior ischemic optic neuropathy. The Westergren sedimentation rate was 66 mm/h. Temporal artery biopsy was consistent with giant cell arteritis. Routine transcranial Doppler testing performed on a Pioneer 2020 instrument (Nicolet Vascular, Inc., Golden, CO) equipped with special software for microembolus detection showed a microembolic signal in the left ophthalmic artery. During a subsequent monitoring study, microembolic signals were detected in the anterior and middle cerebral arteries, bilaterally. Microembolism can occur in giant cell arteritis. Ophthalmic artery microembolism can be detected in vivo by transcranial Doppler ultrasonography. This new imaging capability can potentially be useful when evaluating patients with vascular disorders of the eye.