David Z. Rose

Ischemic stroke after use of the synthetic marijuana “spice”

Objectives: To report and associate acute cerebral infarctions in 2 young, previously healthy siblings with use of the street drug known as “spice” (a synthetic marijuana product, also known as “K2”), which they independently smoked before experiencing acute embolic-appearing ischemic strokes. Methods: We present history, physical examination, laboratory data, cerebrovascular imaging, echocardiogram, ECG, and hospital course of these patients. Results: We found that in both siblings spice was obtained from the same source. The drug was found to contain the schedule I synthetic cannabinoid JWH-018. Full stroke workup was unrevealing of a stroke etiology; urine drug screen was positive for marijuana. Conclusions: We found that our 2 patients who smoked the street drug spice had a temporal association with symptoms of acute cerebral infarction. This association may be confounded by contaminants in the product consumed (i.e., marijuana or an unidentified toxin) or by an unknown genetic mechanism. The imaging of both patients suggests an embolic etiology, which is consistent with reports of serious adverse cardiac events with spice use, including tachyarrhythmias and myocardial infarctions.

Hemorrhagic stroke following use of the synthetic marijuana “spice”

The association between the street drug spice (K-2 or herbal incense), a synthetic marijuana, and intracranial hemorrhage (ICH) has not yet been described, but it has with acute ischemic stroke (AIS),1 seizure, and myocardial infarction.2 Two young patients (31 and 25 years old) independently presented to our hospital with subarachnoid hemorrhage (SAH) after spice inhalation. The first also had 2 large intraparenchymal hemorrhages (IPH); the other also had AIS. Both were previously healthy without hypertension, coagulopathy, bleeding diathesis, thrombocytopenia, intracranial aneurysm, arteriovenous malformation, connective tissue disease, or anticoagulant/antiplatelet medication use.

ASPECTS decay during inter-facility transfer in patients with large vessel occlusion strokes

Background Favorable imaging profile according to the Alberta Stroke Program Early CT Score (ASPECTS) on non-contrast head CT is a key criterion for the selection of patients with ischemic stroke from large vessel occlusion (LVO) for IA revascularization therapies. Objective To analyze factors associated with changes in ASPECTS during inter-hospital transfer and to determine how deterioration of ASPECTS affects eligibility for endovascular procedures. Methods We analyzed factors associated with changes in ASPECTS during inter-hospital transfer and their potential impact on eligibility for IA stroke therapies in patients with anterior circulation ischemic strokes. Clinical and demographic characteristics between patients with favorable (ASPECTS ≥6) and unfavorable (ASPECTS <6) imaging on repeat CT were compared. Results Stroke evolution towards unfavorable ASPECTS occurred in 13/42 (31%) patients who initially had a favorable imaging profile at outside hospitals. A higher National Institutes of Health Stroke Scale (NIHSS) score was the only significant predictor of ASPECTS decay, whereas other clinical characteristics, such as the use of IV thrombolysis and site of LVO, were similar between the two groups. Conclusions In our cohort, one out of three patients became ineligible for IA thrombectomy because of unfavorable ASPECTS ‘decay’ following inter-hospital transfer. Except for NIHSS severity, baseline clinical factors could not identify which patients were at risk for ASPECTS deterioration.

Transcranial Laser Therapy and Infarct Volume

Background and Purpose— Two randomized trials suggested that transcranial laser therapy (TLT) may benefit patients with acute ischemic stroke, although efficacy has not been confirmed. Supportive proof of concept could be demonstrated if TLT reduces the volume of cortical infarction. Methods— The NeuroThera Efficacy and Safety Trial-2 (NEST-2) was a randomized trial of TLT versus sham in patients with acute ischemic stroke treated within 24 hours of onset. Infarct volumes were measured quantitatively and semiquantitatively on all protocol-required computed tomography (or MRI, if clinically indicated) scans performed on day 5 (±2). Two approaches assessed treatment effects on cortex: (1) indirectly, by analyzing total infarct volume among patients with clinical presentations suggesting cortical involvement; and (2) directly, by assessing the cortical Alberta Stroke Program Early CT Score (cASPECTS) components (M1-M6, anterior, posterior) on a 0- to 8-point modified scale. Results— A total of 640 subjects had scans (576 computed tomography, 64 MRI) on day 5. The reliability of ASPECTS (intraclass correlation coefficient=0.85) and cASPECTS (intraclass correlation coefficient=0.82) was excellent, and total ASPECTS was correlated with total infarct volume (r=0.71). In the overall study population, there was no impact of TLT on total infarct volume (P=0.30), total ASPECTS (P=0.85), or cASPECTS (P=0.89). Similarly, no effect was seen in any of the following prespecified subgroups selected to indicate cortical involvement: baseline National Institutes of Health Stroke Scale score >10, Oxfordshire Total Anterior Circulation Syndrome, subjects with aphasia or extinction at baseline, or subjects with radiographic involvement of cortex. Conclusions— TLT was not associated with a reduction in overall or cortical infarct volume as measured on computed tomography in the subacute phase.

Informed Consent: The Rate-Limiting Step in Acute Stroke Trials

Successful implementation of a randomized clinical trial (RCT) for neuro-vascular emergencies such as cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage is extraordinarily challenging. Besides establishing an accurate, hyper-expedited diagnosis among many mimics in a person with acute neurological deficits, informed consent must be obtained from this vulnerable group of patients who may be unable to convey their own wishes, grasp the gravity of their situation, or give a complete history or examination. We review the influences, barriers, and factors investigators encounter when providing established and putative stroke therapies, and focus on informed consent, the most important research protector of human subjects, as the rate-limiting step for enrollment into acute stroke RCTs. The informed consent process has received relatively little attention in the stroke literature, but is especially important for stroke victims with acute cognitive, aural, lingual, motor, or visual impairments. Consent by a surrogate may not accurately reflect the patient’s wishes. Further, confusion about trial methodology, negative opinions of placebo-controlled studies, and therapeutic misconception by patients or surrogates may impede trial enrollment and requires further study. Exception from informed consent offers an opportunity that is rarely if ever utilized for stroke RCTs. Ultimately, advancing the knowledge base and treatment paradigms for acute stroke is essential but autonomy, beneficence (non-malfeasance), and justice must also be carefully interwoven into any well-designed RCT.

Sex Disparities in Ischemic Stroke Care: FL-PR CReSD Study (Florida–Puerto Rico Collaboration to Reduce Stroke Disparities)

Background and Purpose— Sex-specific disparities in stroke care including thrombolytic therapy and early hospital admission are reported. In a large registry of Florida and Puerto Rico hospitals participating in the Get With The Guidelines—Stroke program, we sought to determine sex-specific differences in ischemic stroke performance metrics and overall thrombolytic treatment. Methods— Around 51 317 (49% women) patients were included from 73 sites from 2010 to 2014. Multivariable logistic regression with generalized estimating equations evaluated sex-specific differences in the prespecified Get With The Guidelines—Stroke metrics for defect-free care in ischemic stroke, adjusting for age, race-ethnicity, insurance status, hospital characteristics, individual risk factors, and the presenting stroke severity. Results— As compared with men, women were older (73±15 versus 69±14 years; P<0.0001), more hypertensive (67% versus 63%, P<0.0001), and had more atrial fibrillation (19% versus 16%; P<0.0001). Defect-free care was slightly lower in women than in men (odds ratio, 0.96; 95% confidence interval, 0.93–1.00). Temporal trends in defect-free care improved substantially and similarly for men and women, with a 29% absolute improvement in women (P<0.0001) and 28% in men (P<0.0001), with P value of 0.13 for time-by-sex interaction. Women were less likely to receive thrombolysis (odds ratio, 0.92; 95% confidence interval, 0.86–0.99; P=0.02) and less likely to have a door-to-needle time <1 hour (odds ratio, 0.83; 95% confidence interval, 0.71–0.97; P=0.02) as compared with men. Conclusions— Women received comparable stroke care to men in this registry as measured by prespecified Get With The Guidelines metrics. However, women less likely received thrombolysis and had door-to-needle time <1 hour, an observation that calls for the implementation of interventions to reduce sex disparity in these measures.

Racial-Ethnic Disparities in Acute Stroke Care in the Florida-Puerto Rico Collaboration to Reduce Stroke Disparities Study.

Background Racial‐ethnic disparities in acute stroke care can contribute to inequality in stroke outcomes. We examined race‐ethnic disparities in acute stroke performance metrics in a voluntary stroke registry among Florida and Puerto Rico Get With the Guidelines‐Stroke hospitals. Methods and Results Seventy‐five sites in the Florida Puerto Rico Stroke Registry (66 Florida and 9 Puerto Rico) recorded 58 864 ischemic stroke cases (2010–2014). Logistic regression models examined racial‐ethnic differences in acute stroke performance measures and defect‐free care (intravenous tissue plasminogen activator treatment, in‐hospital antithrombotic therapy, deep vein thrombosis prophylaxis, discharge antithrombotic therapy, appropriate anticoagulation therapy, statin use, smoking cessation counseling) and temporal trends. Among ischemic stroke cases, 63% were non‐Hispanic white (NHW), 18% were non‐Hispanic black (NHB), 14% were Hispanic living in Florida, and 6% were Hispanic living in Puerto Rico. NHW patients were the oldest, followed by Hispanics, and NHBs. Defect‐free care was greatest among NHBs (81%), followed by NHWs (79%) and Florida Hispanics (79%), then Puerto Rico Hispanics (57%) (P<0.0001). Puerto Rico Hispanics were less likely than Florida whites to meet any stroke care performance metric other than anticoagulation. Defect‐free care improved for all groups during 2010–2014, but the disparity in Puerto Rico persisted (2010: NHWs=63%, NHBs=65%, Florida Hispanics=59%, Puerto Rico Hispanics=31%; 2014: NHWs=93%, NHBs=94%, Florida Hispanics=94%, Puerto Rico Hispanics=63%). Conclusions Racial‐ethnic/geographic disparities were observed for acute stroke care performance metrics. Adoption of a quality improvement program improved stroke care from 2010 to 2014 in Puerto Rico and all Florida racial‐ethnic groups. However, stroke care quality delivered in Puerto Rico is lower than in Florida. Sustained support of evidence‐based acute stroke quality improvement programs is required to improve stroke care and minimize racial‐ethnic disparities, particularly in resource‐strained Puerto Rico.

Ischemic stroke after use of the synthetic marijuana “spice”Author Response

We read with interest the article by Freeman et al.1 on synthetic marijuana (spice). It is important that physicians and the lay public know the hazards of this substance, since greater recognition will lead to better diagnosis and treatment. The diagnosis of spice encephalopathy with stroke or seizure1,2 can be challenging because it may mimic some aspects of serotonin syndrome and neuroleptic malignant syndrome and does not have a simple …

Predictors of Thrombolysis Administration in Mild Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities

Background and Purpose— Mild stroke is the most common cause for thrombolysis exclusion in patients acutely presenting to the hospital. Thrombolysis administration in this subgroup is highly variable among different clinicians and institutions. We aim to study the predictors of thrombolysis in patients with mild ischemic stroke in the FL-PR CReSD registry (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities). Methods— Among 73 712 prospectively enrolled patients with a final diagnosis of ischemic stroke or TIA from January 2010 to April 2015, we identified 7746 cases with persistent neurological symptoms and National Institutes of Health Stroke Scale ⩽5 who arrived within 4 hours of symptom onset. Multilevel logistic regression analysis with generalized estimating equations was used to identify independent predictors of thrombolytic administration in the subgroup of patients without contraindications to thrombolysis. Results— We included 6826 cases (final diagnosis mild stroke, 74.6% and TIA, 25.4%). Median age was 72 (interquartile range, 21); 52.7% men, 70.3% white, 12.9% black, 16.8% Hispanic; and median National Institutes of Health Stroke Scale, 2 (interquartile range, 3). Patients who received thrombolysis (n=1281, 18.7%) were younger (68 versus 72 years), had less vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), had lower risk of prior vascular disease (myocardial infarction, peripheral vascular disease, and previous stroke), and had a higher presenting median National Institutes of Health Stroke Scale (4 versus 2). In the multilevel multivariable model, early hospital arrival (arrive by 0–2 hours versus ≥3.5 hours; odds ratio [OR], 8.16; 95% confidence interval [CI], 4.76–13.98), higher National Institutes of Health Stroke Scale (OR, 1.87; 95% CI, 1.77–1.98), aphasia at presentation (OR, 1.35; 95% CI, 1.12–1.62), faster door-to-computed tomography time (OR, 1.81; 95% CI, 1.53–2.15), and presenting to an academic hospital (OR, 2.02; 95% CI, 1.39–2.95) were independent predictors of thrombolysis administration. Conclusions— Mild acutely presenting stroke patients are more likely to receive thrombolysis if they are young, white, or Hispanic and arrive early to the hospital with more severe neurological presentation. Identification of predictors of thrombolysis is important in design of future studies to assess the use of thrombolysis for mild stroke.

Disparities and Trends in Door-to-Needle Time: The FL-PR CReSD Study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities).

Background and Purpose— In the United States, about half of acute ischemic stroke patients treated with tPA (tissue-type plasminogen activator) receive treatment within 60 minutes of hospital arrival. We aimed to determine the proportion of patients receiving tPA within 60 minutes (door-to-needle time [DTNT] ⩽60) and 45 minutes (DTNT ⩽45) of hospital arrival by race/ethnicity and sex and to identify temporal trends in DTNT ⩽60 and DTNT ⩽45. Methods— Among 65 654 acute ischemic stroke admissions in the National Institute of Neurological Disorders and Stroke-funded FL-PR CReSD study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities) from 2010 to 2015, we included 6181 intravenous tPA-treated cases (9.4%). Generalized estimating equations were used to determine predictors of DTNT ⩽60 and DTNT ⩽45. Results— DTNT ⩽60 was achieved in 42% and DTNT ⩽45 in 18% of cases. After adjustment, women less likely received DTNT ⩽60 (odds ratio, 0.81; 95% confidence interval, 0.72–0.92) and DTNT ⩽45 (odds ratio, 0.73; 95% confidence interval, 0.57–0.93). Compared with Whites, Blacks less likely had DTNT ⩽45 during off hours (odds ratio, 0.68; 95% confidence interval, 0.47–0.98). Achievement of DTNT ⩽60 and DTNT ⩽45 was highest in South Florida (50%, 23%) and lowest in West Central Florida (28%, 11%). Conclusions— In the FL-PR CReSD, achievement of DTNT ⩽60 and DTNT ⩽45 remains low. Compared with Whites, Blacks less likely receive tPA treatment within 45 minutes during off hours. Treatment within 60 and 45 minutes is lower in women compared with men and lowest in West Central Florida compared with other Florida regions and Puerto Rico. Further research is needed to identify reasons for delayed thrombolytic treatment in women and Blacks and factors contributing to regional disparities in DTNT.