Ilana Ruff

Acute Stroke Intervention: A Systematic Review

IMPORTANCE Acute ischemic stroke is a major cause of mortality and morbidity in the United States. We review the latest data and evidence supporting catheter-directed treatment for proximal artery occlusion as an adjunct to intravenous thrombolysis in patients with acute stroke. OBJECTIVE To review the pathophysiology of acute brain ischemia and infarction and the evidence supporting various stroke reperfusion treatments. EVIDENCE REVIEW Systematic literature search of MEDLINE databases published between January 1, 1990, and February 11, 2015, was performed to identify studies addressing the role of thrombolysis and mechanical thrombectomy in acute stroke management. Studies included randomized clinical trials, observational studies, guideline statements, and review articles. Sixty-eight articles (N = 108,082 patients) were selected for review. FINDINGS Intravenous thrombolysis is the mainstay of acute ischemic stroke management for any patient with disabling deficits presenting within 4.5 hours from symptom onset. Randomized trials have demonstrated that more patients return to having good function (defined by being independent and having slight disability or less) when treated within 4.5 hours after symptom onset with intravenous recombinant tissue plasminogen activator (IV rtPA) therapy. Mechanical thrombectomy in select patients with acute ischemic stroke and proximal artery occlusions has demonstrated substantial rates of partial or complete arterial recanalization and improved outcomes compared with IV rtPA or best medical treatment alone in multiple randomized clinical trials. Regardless of mode of reperfusion, earlier reperfusion is associated with better clinical outcomes. CONCLUSIONS AND RELEVANCE Intravenous rtPA remains the standard of care for patients with moderate to severe neurological deficits who present within 4.5 hours of symptom onset. Outcomes for some patients with acute ischemic stroke and moderate to severe neurological deficits due to proximal artery occlusion are improved with endovascular reperfusion therapy. Efforts to hasten reperfusion therapy, regardless of the mode, should be undertaken within organized stroke systems of care.

Assessment of the Language Laterality Index in Patients with Brain Tumor Using Functional MR Imaging: Effects of Thresholding, Task Selection, and Prior Surgery

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is used to determine preoperatively the laterality of cortical language representation along with the relationship of language areas to adjacent brain tumors. The purpose of this study was to determine whether changing the statistical threshold for different language tasks influences the language laterality index (LI) for a group of controls, patients with tumor without prior surgery, and patients with tumor and prior surgery. MATERIALS AND METHODS: Seven controls, 9 patients with tumor without prior surgery, and 4 patients with tumor and prior surgery performed verb-generation, phonemic fluency, and semantic fluency language tasks during fMRI. Interhemispheric activation differences between the left and right Broca regions of interest were determined by calculating language LIs. LIs were compared within each group, between groups, and between language tasks. Intraoperative electrocortical mapping or the presence of aphasia during postoperative neurology examinations or both were used as ground truth. RESULTS: The language LI varied as a result of statistical thresholding, presence of tumor, prior surgery, and language task. Although patients and controls followed a similar shape in the LI curve, there was no optimal P value for determining the LI. Three patients demonstrated a shift in the LI between hemispheres as a function of statistical threshold. Verb generation was the least variable task both between tasks and across groups. CONCLUSION: For preoperative patients with tumor, the LI should be examined across a spectrum of P values and a range of tasks to ensure reliability. Our data suggest that the LI may be threshold- and task-dependent, particularly in the presence of adjacent tumor.

Recruitment of Anterior and Posterior Structures in Lexical-Semantic Processing: An fMRI Study Comparing Implicit and Explicit Tasks

Previous studies examining explicit semantic processing have consistently shown activation of the left inferior frontal gyrus (IFG). In contrast, implicit semantic processing tasks have shown activation in posterior areas including the superior temporal gyrus (STG) and the middle temporal gyrus (MTG) with less consistent activation in the IFG. These results raise the question whether the functional role of the IFG is related to those processes needed to make a semantic decision or to processes involved in the extraction and analysis of meaning. This study examined neural activation patterns during a semantic judgment task requiring overt semantic analysis, and then compared these activation patterns to previously obtained results using the same semantically related and unrelated word pairs in a lexical decision task which required only implicit semantic processing (Rissman, J., Eliassen, J. C., & Blumstein, S. E. (2003). An event-related fMRI investigation of implicit semantic priming. Journal of Cognitive Neuroscience, 15, 1160-1175). The behavioral results demonstrated that the tasks were equivalent in difficulty. fMRI results indicated that the IFG and STG bilaterally showed greater activation for semantically unrelated than related word pairs across the two tasks. Comparison of the two task types across conditions revealed greater activation for the semantic judgment task only in the STG bilaterally and not in the IFG. These results suggest that the pre-frontal cortex is recruited similarly in the service of both the lexical decision and semantic judgment tasks. The increased activation in the STG in the semantic judgment task reflects the greater depth of semantic processing required in this task and indicates that the STG is not simply a passive store of lexical-semantic information but is involved in the active retrieval of this information.

Improving Door-to-Needle Times A Single Center Validation of the Target Stroke Hypothesis

Background and Purpose— National guidelines recommend imaging within 25 minutes of emergency department arrival and intravenous tissue-type plasminogen activator within 60 minutes of emergency department arrival for patients with acute stroke. In 2007, we implemented a new institutional acute stroke care model to include 10 best practices and evaluated the effect of this intervention on improving door-to-computed tomography (CT) and door-to-needle (DTN) times at our hospital. Methods— We compared patients who presented directly to our hospital with acute ischemic stroke in the preintervention (2003–2006) and postintervention (2008–2011) periods. We did not include 2007, the year that the new protocol was established. Predictors of DTN ⩽60 minutes before and after the intervention were assessed using &khgr;2 for categorical variables, and t test and Wilcoxon signed-rank test for continuous variables. Results— Among 2595 patients with acute stroke, 284 (11%) received intravenous tissue-type plasminogen activator. For patients arriving within an intravenous tissue-type plasminogen activator window, door-to-CT <25 improved from 26.7% pre intervention to 52.3% post intervention (P<0.001). Similarly, the percentage of patients with DTN <60 doubled from 32.4% to 70.3% (P<0.001). Patients with DTN ⩽60 did not differ significantly with respect to demographics, comorbidities, or National Institutes of Health Stroke Scale score in comparison with those treated after 60 minutes. Conclusions— Door-to-CT and DTN times improved dramatically after applying 10 best practices, all of which were later incorporated into the Target Stroke Guidelines created by the American Heart Association. The only factor that significantly affected DTN60 was the intervention itself, indicating that these best practices can result in improved DTN times.

Do efforts to decrease door-to-needle time risk increasing stroke mimic treatment rates?

SummaryAn unintended consequence of rapid thrombolysis may be more frequent treatment of stroke mimics, nonvascular conditions that simulate stroke. We explored the relationship between door-to-needle (DTN) times and thrombolysis of stroke mimics at a single academic center by analyzing consecutive quartiles of patients who were treated with IV tissue plasminogen activator for suspected stroke from January 1, 2010 to February 28, 2014. An increase in the proportion of stroke mimic patients (6.7% in each of the 1st and 2nd, 12.9% in the 3rd, and 30% in the last consecutive case quartile; p = 0.03) and a decrease in median DTN time from 89 to 56 minutes (p < 0.01) was found. As more centers reduce DTN times, the rates of stroke mimic treatment should be carefully monitored.

Predictors of naming decline after dominant temporal lobectomy: age at onset of epilepsy and age of word acquisition.

This study examined factors affecting object naming decline in patients who have undergone anterior temporal lobectomy (ATL) and the correlation between age of word acquisition and loss of specific object names postoperatively. The Boston Naming Test (BNT) was used to assess changes in object-naming performance in patients who underwent ATL. Correlation analyses were performed by group (dominant or nondominant ATL) on individual items from the BNT to determine if age of acquisition of object names had an effect on postoperative word loss. The influence of age at onset of seizures on naming decline was examined in the dominant ATL group. Only patients who had undergone dominant ATL experienced significant clinical and statistical declines after surgery. Among the patients who underwent dominant ATL, those with late age at onset of seizures declined significantly more than those with early-onset seizures. When individual object names were examined, age of acquisition of words predicted whether words were lost or gained after surgery.

Quality of life in patients with TIA and minor ischemic stroke.

Objective: We investigated health-related quality of life (HRQOL) in patients with TIA and minor ischemic stroke (MIS) using Neuro-QOL, a validated, patient-reported outcome measurement system. Methods: Consecutive patients with TIA or MIS who had (1) modified Rankin Scale (mRS) score of 0 or 1 at baseline, (2) initial NIH Stroke Scale score of ≤5, (3) no acute reperfusion treatment, and (4) 3-month follow-up, were recruited. Recurrent stroke, disability by mRS and Barthel Index, and Neuro-QOL scores in 5 prespecified domains were prospectively recorded. We assessed the proportion of patients with impaired HRQOL, defined as T scores more than 0.5 SD worse than the general population average, and identified predictors of impaired HRQOL using logistic regression. Results: Among 332 patients who met study criteria (mean age 65.7 years, 52.4% male), 47 (14.2%) had recurrent stroke within 90 days and 41 (12.3%) were disabled (mRS >1 or Barthel Index <95) at 3 months. Any HRQOL impairment was noted in 119 patients (35.8%). In multivariate analysis, age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01–1.04), initial NIH Stroke Scale score (adjusted OR 1.39, 95% CI 1.17–1.64), recurrent stroke (adjusted OR 2.10, 95% CI 1.06–4.13), and proxy reporting (adjusted OR 3.94, 95% CI 1.54–10.10) were independent predictors of impaired HRQOL at 3 months. Conclusions: Impairment in HRQOL is common at 3 months after MIS and TIA. Predictors of impaired HRQOL include age, index stroke severity, and recurrent stroke. Future studies should include HRQOL measures in outcome assessment, as these may be more sensitive to mild deficits than traditional disability scales.

Diagnostic Yield of Pelvic Magnetic Resonance Venography in Patients With Cryptogenic Stroke and Patent Foramen Ovale

Background and Purpose— Paradoxical embolization is frequently posited as a mechanism of ischemic stroke in patients with patent foramen ovale. Several studies have suggested that the deep lower extremity and pelvic veins might be an embolic source in cryptogenic stroke (CS) patients with patent foramen ovale. Methods— Consecutive adult patients with ischemic stroke or transient ischemic attack and a patent foramen ovale who underwent pelvic magnetic resonance venography as part of an inpatient diagnostic evaluation were included in this single-center retrospective observational study to determine pelvic and lower extremity (LE) deep venous thrombosis (DVT) prevalence in CS versus non-CS stroke subtypes. Results— Of 131 patients who met inclusion criteria, 126 (96.2%) also had LE duplex ultrasound data. DVT prevalence overall was 7.6% (95% confidence interval, 4.1–13.6), pelvic DVT 1.5% (95% confidence interval, 0.1–5.8), and LE DVT 7.1% (95% confidence interval, 3.6–13.2). One patient with a pelvic DVT also had a LE DVT. Comparing patients with CS (n=98) with non-CS subtypes (n=33), there was no significant difference in the prevalence of pelvic DVT (2.1% versus 0%, P=1), LE DVT (6.2% versus 10.3%, P=0.43), or any DVT (7.2% versus 9.1%, P=0.71). Conclusions— Among patients with ischemic stroke/transient ischemic attack and patent foramen ovale, the majority of detected DVTs were in LE veins rather than the pelvic veins and did not differ by stroke subtype. The routine inclusion of pelvic magnetic resonance venography in the diagnostic evaluation of CS warrants further prospective investigation.

A resident boot camp for reducing door-to-needle times at academic medical centers

Background: We sought to determine if a structured educational program for neurology residents can lower door-to-needle (DTN) times at an academic institution. Methods: A neurology resident educational stroke boot camp was developed and implemented in April 2013. Using a prospective database of 170 consecutive acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA) in our emergency department (ED), we evaluated the effect of the intervention on DTN times. We compared DTN times and other process measures preintervention and postintervention. p Values < 0.05 were considered significant. Results: The proportion of AIS patients treated with tPA within 60 minutes of arrival to our ED tripled from 18.1% preintervention to 61.2% postintervention (p < 0.001) with concomitant reduction in DTN time (median 79 minutes vs 58 minutes, p < 0.001). The resident-delegated task (stroke code to tPA) was reduced (75 minutes vs 44 minutes, p < 0.001), while there was no difference in ED-delegated tasks (door to stroke code [7 minutes vs 6 minutes, p = 0.631], door to CT [18 minutes in both groups, p = 0.547]). There was an increase in stroke mimics treated (6.9% vs 18.4%, p = 0.031), which did not lead to an increase in adverse outcomes. Conclusions: DTN times were reduced after the implementation of a stroke boot camp and were driven primarily by efficient resident stroke code management. Educational programs should be developed for health care providers involved in acute stroke patient care to improve rapid access to IV tPA at academic institutions.

Clinical Reasoning: A 21-year-old woman with right eye swelling and bruising

A 21-year-old woman presented with right eye swelling and bruising. Several weeks prior to admission, she had bifrontal headaches associated with a “whooshing” pulsation in her right ear. She went to a local emergency department where CT scan of the brain was read as negative. One week later, she noticed that her right eye was turned toward her nose. She denied diplopia. On the day of admission, she awoke and noticed bruising under her right eye accompanied by swelling. She also had blurry vision. Her physical examination was remarkable for right eye ptosis, conjunctival injection, and mild proptosis with ecchymosis above and below the eye (figure 1). She was unable to abduct her right eye past midline, visual acuity was 20/30 bilaterally, and her visual fields were intact. There was an ocular bruit auscultated over the right eye. Figure 1 Initial external eye findings Right eye ptosis with proptosis, conjunctival injection, and ecchymosis surrounding the right eye. ### Questions for consideration: 1. What other history is important to obtain? 2. What is the differential diagnosis? The patient denied any history of trauma. Her past medical history was significant for Ehlers-Danlos type IV, complicated by bowel rupture 6 years prior, necessitating subtotal colectomy and colostomy. She also had chronic migraine and corrective surgery for amblyopia as a child. Family history was significant for her mother who died at age 35 of splenic rupture and maternal grandmother who died at age 43 of subarachnoid hemorrhage. The differential diagnosis included thyroid ophthalmopathy, tumor, infection, inflammation (e.g., Tolosa-Hunt), and carotid cavernous aneurysm or fistula. ### Question for consideration: 1. What further testing should be considered? Magnetic resonance angiography revealed enlarged superior ophthalmic veins bilaterally, right greater than left, with an increased prominence in the right cavernous sinus (figure 2, A and B). The patient was diagnosed with carotid cavernous fistula. She was sent to the ophthalmology clinic where her intraocular …