Joshua A. Hirsch

Recommendations on Angiographic Revascularization Grading Standards for Acute Ischemic Stroke A Consensus Statement

See related article, p 2509 Intra-arterial therapy (IAT) for acute ischemic stroke (AIS) has dramatically evolved during the past decade to include aspiration and stent-retriever devices. Recent randomized controlled trials have demonstrated the superior revascularization efficacy of stent-retrievers compared with the first-generation Merci device.1,2 Additionally, the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) 2, the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and the Interventional Management of Stroke (IMS) III trials have confirmed the importance of early revascularization for achieving better clinical outcome.3–5 Despite these data, the current heterogeneity in cerebral angiographic revascularization grading (CARG) poses a major obstacle to further advances in stroke therapy. To date, several CARG scales have been used to measure the success of IAT.6–14 Even when the same scale is used in different studies, it is applied using varying operational criteria, which further confounds the interpretation of this key metric.10 The lack of a uniform grading approach limits comparison of revascularization rates across clinical trials and hinders the translation of promising, early phase angiographic results into proven, clinically effective treatments.6–14 For these reasons, it is critical that CARG scales be standardized and end points for successful revascularization be refined.6 This will lead to a greater understanding of the aspects of revascularization that are strongly predictive of clinical response. The optimal grading scale must demonstrate (1) a strong correlation with clinical outcome, (2) simplicity and feasibility of scale interpretation while ensuring characterization of relevant angiographic findings, and (3) high inter-rater reproducibility. To address these issues, a multidisciplinary panel of neurointerventionalists, neuroradiologists, and stroke neurologists with extensive experience in neuroimaging and IAT, convened at the “Consensus Meeting on Revascularization Grading Following Endovascular Therapy” with the goal …

fMRI reveals large-scale network activation in minimally conscious patients

Background: The minimally conscious state (MCS) resulting from severe brain damage refers to a subset of patients who demonstrate unequivocal, but intermittent, behavioral evidence of awareness of self or their environment. Although clinical examination may suggest residual cognitive function, neurobiological correlates of putative cognition in MCS have not been demonstrated. Objective: To test the hypothesis that MCS patients retain active cerebral networks that underlie cognitive function even though command following and communication abilities are inconsistent. Methods: fMRI was employed to investigate cortical responses to passive language and tactile stimulation in two male adults with severe brain injuries leading to MCS and in seven healthy volunteers. Results: In the case of the patient language-related tasks, auditory stimulation with personalized narratives elicited cortical activity in the superior and middle temporal gyrus. The healthy volunteers imaged during comparable passive language stimulation demonstrated responses similar to the patients’ responses. However, when the narratives were presented as a time-reversed signal, and therefore without linguistic content, the MCS patients demonstrated markedly reduced responses as compared with volunteer subjects, suggesting reduced engagement for “linguistically” meaningless stimuli. Conclusions: The first fMRI maps of cortical activity associated with language processing and tactile stimulation of patients in the minimally conscious state (MCS) are presented. These findings of active cortical networks that serve language functions suggest that some MCS patients may retain widely distributed cortical systems with potential for cognitive and sensory function despite their inability to follow simple instructions or communicate reliably.

MRI-Based Selection for Intra-Arterial Stroke Therapy Value of Pretreatment Diffusion-Weighted Imaging Lesion Volume in Selecting Patients With Acute Stroke Who Will Benefit From Early Recanalization

Background and Purpose— Recent studies demonstrate that an acute diffusion-weighted imaging lesion volume >70 cm3 predicts poor outcome in patients with stroke. We sought to determine if this threshold could identify patients treated with intra-arterial therapy who would do poorly despite reperfusion. In patients with initial infarcts <70 cm3, we sought to determine what effect recanalization and time to recanalization had on infarct growth and functional outcome. Methods— We retrospectively studied 34 consecutive patients with anterior circulation stroke who underwent pretreatment diffusion-weighted imaging and perfusion-weighted imaging and subsequent intra-arterial therapy. Recanalization success and time to recanalization were recorded. Initial diffusion-weighted imaging and mean transit time lesion and final infarct volumes were determined. Patients were stratified based on initial infarct volume, recanalization status, and time to recanalization. Statistical tests were performed to assess differences in clinical and imaging outcomes. Good clinical outcome was defined as a 3-month modified Rankin Scale score ≤2. Results— Among patients with initial infarcts >70 cm3, all had poor outcomes despite a 50% recanalization rate with mean infarct growth of 114 cm3. These patients also had the largest mean transit time volumes (P<0.04). Patients with initial infarct volumes <70 cm3 who recanalized early had the best clinical outcomes (P<0.008) with a 64% rate of modified Rankin Scale score ≤2 and the least infarct growth (P<0.03) with mean growth of 18 cm3. Conclusion— This study supports the use of an acute diffusion-weighted imaging lesion volume threshold as an imaging selection criterion for intra-arterial therapy. It also confirms the importance of early reperfusion in selected patients.

Quantitative objective markers for upper and lower motor neuron dysfunction in ALS

Objective: To investigate the value of objective biomarkers for upper (UMN) and lower (LMN) motor neuron involvement in ALS. Methods: We prospectively studied 64 patients with ALS and its subsets using clinical measures, proton MR spectroscopic imaging (1H MRSI), diffusion tensor imaging, transcranial magnetic stimulation, and the motor unit number estimation (MUNE) at baseline and every 3 months for 15 months and compared them with control subjects. Results: 1H MRSI measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration were markedly reduced in ALS (p = 0.009) and all UMN syndromes combined (ALS, familial ALS [fALS], and primary lateral sclerosis; p = 0.03) vs control values. Central motor conduction time to the tibialis anterior was prolonged in ALS (p < 0.0005) and combined UMN syndromes (p = 0.001). MUNE was lower in ALS (p < 0.0005) and all LMN syndromes combined (ALS, fALS, and progressive muscular atrophy; p = 0.001) vs controls. All objective markers correlated well with the ALS Functional Rating Scale–Revised, finger and foot tapping, and strength testing, suggesting these markers related to disease activity. Regarding changes over time, MUNE changed rapidly, whereas neuroimaging markers changed more slowly and did not significantly differ from baseline. Conclusions: 1H MR spectroscopic imaging measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration and ratio of NAA to creatine, central motor conduction time to the tibialis anterior, and motor unit number estimation significantly differed between ALS, its subsets, and control subjects, suggesting they have potential to provide insight into the pathobiology of these disorders.

Preliminary Experience with Onyx Embolization for the Treatment of Intracranial Dural Arteriovenous Fistulas

BACKGROUND AND PURPOSE: Onyx was recently approved for the treatment of pial arteriovenous malformations, but its use to treat dural arteriovenous fistulas (DAVFs) is not yet well established. We now report on the treatment of intracranial DAVFs using this nonadhesive liquid embolic agent. MATERIALS AND METHODS: We performed a retrospective analysis of 12 consecutive patients with intracranial DAVFs who were treated with Onyx as the single treatment technique at our institution between March 2006 and February 2007. RESULTS: A total of 17 procedures were performed in 12 patients. In all of the cases, transarterial microcatheterization was performed, and Onyx-18 or a combination of Onyx-18/Onyx-34 was used. Eight patients were men. The mean age was 56 ± 12 years. Nine patients were symptomatic. There was an average of 5 feeders per DAVF (range, 1–9). Cortical venous reflux was present in all of the cases except for 1 of the symptomatic patients. Complete resolution of the DAVF on immediate posttreatment angiography was achieved in 10 patients. The remaining 2 patients had only minimal residual shunting postembolization, 1 of whom appeared cured on a follow-up angiogram 8 weeks later. The other patient has not yet had angiographic follow-up. Follow-up angiography (mean, 4.4 months) is currently available in 9 patients. There was 1 angiographic recurrence (asymptomatic), which was subsequently re-embolized with complete occlusion of the fistula and its draining vein. There was no significant morbidity or mortality. CONCLUSION: In our experience, the endovascular treatment of intracranial DAVFs with Onyx is feasible, safe, and highly effective with a small recurrence rate in the short-term follow-up.

Infarct Volume Is a Pivotal Biomarker After Intra-Arterial Stroke Therapy

Background and Purpose— Pretreatment infarct volume appears to predict clinical outcome after intra-arterial therapy. To confirm the importance of infarct size in patients undergoing intra-arterial therapy, we sought to characterize the relationship between final infarct volume (FIV) and long-term functional outcome in a prospective cohort of endovascularly treated patients. Methods— From our prospective intra-arterial therapy database, we identified 107 patients with acute ischemic stroke with anterior circulation proximal artery occlusions who underwent final infarct imaging and had 3-month modified Rankin Scale scores. Clinical, imaging, treatment, and outcome data were analyzed. Results— Mean age was 66.6 years. Median admission National Institutes of Health Stroke Scale score was 17. Reperfusion (Thrombolysis In Cerebral Infarction 2A–3) was achieved in 78 (72.9%) patients. Twenty-seven (25.2%) patients achieved a 3-month good outcome (modified Rankin Scale 0–2), and 30 (28.0%) died. Median FIV was 71.4 cm3. FIV independently correlated with functional outcome across the entire modified Rankin Scale. In receiver operating characteristic analysis, it was the best discriminator of both good outcome (area under the curve=0.857) and mortality (area under the curve=0.772). A FIV of approximately 50 cm3 demonstrated the greatest accuracy for distinguishing good versus poor outcome, and a FIV of approximately 90 cm3 was highly specific for a poor outcome. The interaction term between FIV and age was the only independent predictor of good outcome (P<0.0001). The impact of FIV was accentuated in patients <80 years. Conclusions— Among patients with anterior circulation acute ischemic stroke who undergo intra-arterial therapy, final infarct volume is a critical determinant of 3-month functional outcome and appears suitable as a surrogate biomarker in proof-of-concept intra-arterial therapy trials.

Malignant CTA Collateral Profile Is Highly Specific for Large Admission DWI Infarct Core and Poor Outcome in Acute Stroke

“Malignant” stroke features include a large core (>100 ml), little penumbra, and no collateral circulation, and portray a poor outcome. These authors studied patients with proximal intracranial arterial occlusions and assessed infarct core size and collateral circulation as seen on CTA. After analyzing 197 such patients, they determined that those with poor collateral grades (absent collateral circulation) had larger infarct cores, large lesions on DWI, and a poor functional outcome. Additionally, patients with poor collaterals had higher NIHSS scores at admission. BACKGROUND AND PURPOSE: Large admission DWI lesion volumes are associated with poor outcomes despite acute stroke treatment. The primary aims of our study were to determine whether CTA collaterals correlate with admission DWI lesion volumes in patients with AIS with proximal occlusions, and whether a CTA collateral profile could identify large DWI volumes with high specificity. MATERIALS AND METHODS: We studied 197 patients with AIS with M1 and/or intracranial ICA occlusions. We segmented admission and follow-up DWI lesion volumes, and categorized CTA collaterals by using a 5-point CS system. ROC analysis was used to determine CS accuracy in predicting DWI lesion volumes >100 mL. Patients were dichotomized into 2 categories: CS = 0 (malignant profile) or CS>0. Univariate and multivariate analyses were performed to compare imaging and clinical variables between these 2 groups. RESULTS: There was a negative correlation between CS and admission DWI lesion volume (ρ = −0.54, P < .0001). ROC analysis revealed that CTA CS was a good discriminator of DWI lesion volume >100 mL (AUC = 0.84, P < .001). CS = 0 had 97.6% specificity and 54.5% sensitivity for DWI volume >100 mL. CS = 0 patients had larger mean admission DWI volumes (165.8 mL versus 32.7 mL, P < .001), higher median NIHSS scores (21 versus 15, P < .001), and were more likely to become functionally dependent at 3 months (95.5% versus 64.0%, P = .003). Admission NIHSS score was the only independent predictor of a malignant CS (P = .007). CONCLUSIONS: In patients with AIS with PAOs, CTA collaterals correlate with admission DWI infarct size. A malignant collateral profile is highly specific for large admission DWI lesion size and poor functional outcome.

Endovascular Approaches to Acute Stroke, Part 1: Drugs, Devices, and Data

SUMMARY: Despite years of research and pioneering clinical work, stroke remains a massive public health concern. Since 1996, we have lived in the era of US Food and Drug Administration−approved intravenous (IV) recombinant tissue plasminogen activator (rtPA). This treatment, despite its promise, continues to exhibit its limitations. Endovascular therapy has several theoretic advantages over IV rtPA, including site specificity, longer treatment windows, and higher recanalization rates. In this article, we will review the various pharmacologic strategies for acute stroke treatment, providing both a historic context and the state of the art. The drugs will be classified on the basis of their theoretic rationale for therapy. Next, we will review the various devices and strategies for mechanical revascularization with an aim toward comprehensiveness. These range from wire disruption of thrombus to preclinical trials for novel mechanical solutions. This first installment of this 2-part series will end with an analysis of retrograde reperfusion techniques.

Epidemiology of low back pain in adults.

Low back pain affects many individuals. It has profound effects on well‐being and is often the cause of significant physical and psychological health impairments. Low back pain also affects work performance and social responsibilities, such as family life, and is increasingly a major factor in escalating health‐care costs. A global review of the prevalence of low back pain in the adult general population has shown its point prevalence to be approximately 12%, with a one‐month prevalence of 23%, a one‐year prevalence of 38%, and a lifetime prevalence of approximately 40%. Furthermore, as the population ages over the coming decades, the number of individuals with low back pain is likely to increase substantially. This comprehensive review is undertaken to assess the increasing prevalence of low back pain and the influence of comorbid factors, along with escalating costs.

Endovascular Approaches to Acute Stroke, Part 2: A Comprehensive Review of Studies and Trials

SUMMARY: Reperfusion remains the mainstay of acute ischemic stroke treatment. Endovascular therapy has become a promising alternative for patients who are ineligible for or have failed intravenous (IV) thrombolysis. The conviction that recanalization of properly selected patients is essential for the achievement of good clinical outcomes has led to the rapid and widespread growth in the adoption of endovascular stroke therapies. However, comparisons of the recent reperfusion studies have brought into question the strength of the association between revascularization and improved clinical outcome. Despite higher rates of recanalization, the mechanical thrombectomy studies have demonstrated substantially lower rates of good outcomes compared with IV and/or intra-arterial thrombolytic trials. However, such analyses disregard important differences in clot location and burden, baseline stroke severity, time from stroke onset to treatment, and patient selection in these studies. Many clinical trials are testing novel devices and drugs as well as the paradigm of physiology-based stroke imaging as a treatment-selection tool. The objective of this article is to provide a comprehensive review of the relevant past, current, and upcoming data on endovascular stroke therapy with a special focus on the prospective studies and randomized clinical trials.