Benefits of GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists for Stroke Reduction in Type 2 Diabetes: A Call to Action for Neurologists.

People living with diabetes are at higher risk for stroke and have a poorer prognosis following a stroke event than those without diabetes. Data from cardiovascular outcome trials and meta-analyses indicate that GLP-1RAs (glucagon-like peptide 1 receptor agonists) reduce the risk of stroke in individuals with type 2 diabetes. Accordingly, many guidelines now recommend the addition of GLP-1RAs to ongoing antihyperglycemic regimens to lower the risk of stroke in type 2 diabetes. The current work summarizes evidence supporting the use of GLP-1RAs for stroke reduction in people with type 2 diabetes and offers 2 new resources for neurologists who are considering GLP-1RAs for their patients-a list of frequently asked questions with evidence-based answers on safely initiating and managing GLP-1RAs, and a practical decision-making algorithm to assist in using GLP-1RAs as part of a stroke reduction strategy.

SLEAP SMART (Sleep Apnea Screening Using Mobile Ambulatory Recorders After TIA/Stroke): A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Poststroke/transient ischemic attack obstructive sleep apnea (OSA) is prevalent, linked with numerous unfavorable health consequences, but remains underdiagnosed. Reasons include patient inconvenience and costs associated with use of in-laboratory polysomnography (iPSG), the current standard tool. Fortunately, home sleep apnea testing (HSAT) can accurately diagnose OSA and is potentially more convenient and cost-effective compared with iPSG. Our objective was to assess whether screening for OSA in patients with stroke/transient ischemic attack using HSAT, compared with standard of care using iPSG, increased diagnosis and treatment of OSA, improved clinical outcomes and patient experiences with sleep testing, and was a cost-effective approach. METHODS: We consecutively recruited 250 patients who had sustained a stroke/transient ischemic attack within the past 6 months. Patients were randomized (1:1) to use of (1) HSAT versus (2) iPSG. Patients completed assessments and questionnaires at baseline and 6-month follow-up appointments. Patients diagnosed with OSA were offered continuous positive airway pressure. The primary outcome was compared between study arms via an intention-to-treat analysis. RESULTS: At 6 months, 94 patients completed HSAT and 71 patients completed iPSG. A significantly greater proportion of patients in the HSAT arm were diagnosed with OSA (48.8% versus 35.2%, P=0.04) compared with the iPSG arm. Furthermore, patients assigned to HSAT, compared with iPSG, were more likely to be prescribed continuous positive airway pressure (40.0% versus 27.2%), report significantly reduced sleepiness, and a greater ability to perform daily activities. Moreover, a significantly greater proportion of patients reported a positive experience with sleep testing in the HSAT arm compared with the iPSG arm (89.4% versus 31.1%). Finally, a cost-effectiveness analysis revealed that HSAT was economically attractive for the detection of OSA compared with iPSG. CONCLUSIONS: In patients with stroke/transient ischemic attack, use of HSAT compared with iPSG increases the rate of OSA diagnosis and treatment, reduces daytime sleepiness, improves functional outcomes and experiences with sleep testing, and could be an economically attractive approach. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02454023.

Lithium Carbonate in a Poststroke Population: Exploratory Analyses of Neuroanatomical and Cognitive Outcomes.

PURPOSE/BACKGROUND: Loss of gray matter after stroke has been associated with cognitive impairment. This pilot study aimed to investigate the therapeutic potential of lithium, a putative neurotrophic agent, in the stroke recovery process within a year of stroke occurrence. METHODS: Twelve stroke patients (mean ± SD age, 71.1 ± 11.9 years) were recruited to the study, and eligible participants were prescribed open-label lithium for 60 days. Magnetic resonance imaging was used to assess global gray matter at baseline and end of treatment; global cognition was assessed using the standardized Mini-Mental State Examination and Montreal Cognitive Assessment, and verbal memory was evaluated using the Hopkins Verbal Learning Test-Revised. FINDINGS/RESULTS: There was no difference in global gray matter volume between baseline and follow-up (t = 1.977, P = 0.074). There was a significant interaction between higher lithium dose and increased global gray matter volume (F = 14.25, P = 0.004) and a correlation between higher lithium dose and improved verbal memory (r = 0.576, P = 0.05). IMPLICATIONS/CONCLUSIONS: Lithium pharmacotherapy may be associated with gray matter volume change and verbal memory improvement in stroke patients, providing a rationale for future trials assessing therapeutic potential of lithium in a poststroke population.

Carotid near-occlusion can be identified with ultrasound by low flow velocity distal to the stenosis.

BACKGROUND: Most carotid near-occlusions are indistinguishable from conventional ≥ 50% stenosis on ultrasound, demonstrating high peak systolic velocity (PSV) in the stenosis. PURPOSE: To study whether the velocity distal to the stenosis can separate high PSV near-occlusion from conventional ≥ 50% stenosis. MATERIAL AND METHODS: We included patients with ≥ 50% carotid stenosis with high PSV (≥125 cm/s), examined with both computed tomography angiography (CTA) and ultrasound within 30 days, and a distal velocity measurement was performed. Based on CTA, cases were divided into three groups: conventional stenosis; near-occlusion without full collapse (NwoC; normal-appearing albeit small distal artery); and near-occlusion with full collapse (NwC; threadlike distal artery). Distal Doppler ultrasound flow velocities were compared between these groups. RESULTS: Sixty patients were included: 33 patients with conventional stenosis; 20 patients with NwoC; and seven patients with NwC. Mean distal PSV was 93, 63, and 21 cm/s ( P < 0.001) and mean distal end-diastolic velocity was 30, 24, and 5 cm/s ( P < 0.001), respectively. A distal PSV < 50 cm/s was 63% sensitive and 94% specific for separating both types of near-occlusion from conventional stenosis. CONCLUSION: In high PSV carotid stenoses, the distal velocity was lower in near-occlusions than conventional carotid stenosis. Distal velocities warrant further investigation in diagnostic studies.

Carotid near-occlusion frequently has high peak systolic velocity on Doppler ultrasound.

PURPOSE: Carotid near-occlusion is a tight atherosclerotic stenosis of the internal carotid artery (ICA) resulting in decrease in diameter of the vessel lumen distal to the stenosis. Near-occlusions can be classified as with or without full collapse, and may have high peak systolic velocity (PSV) across the stenosis, mimicking conventional > 50% carotid artery stenosis. We aimed to determine how frequently near-occlusions have high PSV in the stenosis and determine how accurately carotid Doppler ultrasound can distinguish high-velocity near-occlusion from conventional stenosis. METHODS: Included patients had near-occlusion or conventional stenosis with carotid ultrasound and CT angiogram (CTA) performed within 30 days of each other. CTA examinations were analyzed by two blinded expert readers. Velocities in the internal and common carotid arteries were recorded. Mean velocity, pulsatility index, and ratios were calculated, giving 12 Doppler parameters for analysis. RESULTS: Of 136 patients, 82 had conventional stenosis and 54 had near-occlusion on CTA. Of near-occlusions, 40 (74%) had high PSV (≥ 125 cm/s) across the stenosis. Ten Doppler parameters significantly differed between conventional stenosis and high-velocity near-occlusion groups. However, no parameter was highly sensitive and specific to separate the groups. CONCLUSION: Near-occlusions frequently have high PSV across the stenosis, particularly those without full collapse. Carotid Doppler ultrasound does not seem able to distinguish conventional stenosis from high-velocity near-occlusion. These findings question the use of ultrasound alone for preoperative imaging evaluation.

Unattended Hospital and Home Sleep Apnea Testing Following Cerebrovascular Events.

BACKGROUND: Home sleep apnea testing (HSAT) is an alternative to polysomnography for the detection of obstructive sleep apnea (OSA). We assessed the feasibility of HSAT as an unattended screening tool for patients with a stroke or transient ischemic attack (TIA). AIMS: The primary outcome was the feasibility of unattended HSAT, as defined by analyzability of the data. Secondary outcomes included determining (1) predictors of obtaining nonanalyzable sleep data and (2) time to OSA detection and continuous positive airway pressure (CPAP) initiation. METHODS: In this single-center prospective observational study, inpatients or outpatients who had sustained a stroke or TIA were screened for OSA using the ApneaLink Plus ambulatory sleep monitor in their home or hospital room. RESULTS: There were 102 patients who completed unattended sleep monitoring. Mean age was 68.7 ± 13.7 years, 55.9% were male, 57.8% were outpatients, and 77.5% had a stroke (22.5% with TIA). Eighty-two (80.4%) patients obtained four or more hours of analyzable sleep data. Functional dependence (defined as a modified Rankin Scale of >2) and elevated body mass index were independently associated with obtaining nonanalyzable data. OSA was detected in 63.4% (52 of 82) of patients and, of those, 34 of 52 (65.4%) initiated CPAP therapy. The mean time from study recruitment to HSAT was 1.7 days (median: 1, interquartile range [IQR]: 2) and CPAP was initiated on average within 62.7 days of recruitment (median: 53, IQR: 30). CONCLUSIONS: Unattended HSAT can be feasibly implemented after stroke or TIA. This method facilitates rapid diagnosis and management of OSA in both the outpatient and inpatient settings.

Identifying obstructive sleep apnea after stroke/TIA: evaluating four simple screening tools.

OBJECTIVE: Despite its high prevalence and unfavorable clinical consequences, obstructive sleep apnea (OSA) often remains underappreciated after cerebrovascular events. The purpose of our study was to evaluate the clinical utility of four simple paper-based screening tools for excluding OSA after stroke or transient ischemic attack (TIA). PATIENTS/METHODS: Sixty-nine inpatients and outpatients with stroke or TIA during the past 180 days completed the 4-Variable screening tool (4V), STOP-BAG questionnaire (ie, STOP-BANG questionnaire without the neck circumference measurement), Berlin questionnaire, and the Sleep Obstructive apnea score optimized for Stroke (SOS). They subsequently underwent objective testing using a portable sleep monitoring device. Cutoffs were selected to maximize sensitivity and exclude OSA (AHI ≥ 10) in ≥10% of the cohort. RESULTS: The mean age was 68.3 ± 14.2 years and 47.8% were male. Thirty-two patients (46.4%) were found to have OSA. Male sex, body mass index (BMI), and atrial fibrillation were independent predictors of OSA. Among the screening tools, the 4V had the greatest area under the curve (AUC) of 0.688 (p = 0.007); the sensitivity was 96.9% for a cutoff of <6. The STOP-BAG also significantly detected OSA with an AUC of 0.677 (p = 0.012); the sensitivity was 93.8% for a cutoff of <2. Scores on the 4V and STOP-BAG were significantly correlated with the AHI. CONCLUSIONS: The 4V and STOP-BAG questionnaire may aid clinicians with ruling out OSA within 180 days of stroke/TIA. Due to the atypical presentation of poststroke/TIA OSA, these tools are only moderately predictive; objective testing should still be used for OSA diagnosis in this population.

Orthostatic hypotension, cerebral hypoperfusion, and visuospatial deficits in Lewy body disorders.

BACKGROUND: Orthostatic hypotension and cognitive impairment are two non-motor attributes of Lewy body spectrum disorders that impact independence. This proof-of-concept study examined cerebral blood flow (perfusion) as a mediator of orthostatic hypotension and cognition. METHODS: In fifteen patients with Lewy body disorders, we estimated regional perfusion using pseudo-continuous arterial spin labeling MRI, and quantified orthostatic hypotension from the change in systolic blood pressure between supine and standing positions. Executive, visuospatial, attention, memory, and language domains were characterized by neuropsychological tests. A matching sample of non-demented adults with cerebral small vessel disease was obtained to contrast perfusion patterns associated with comorbid vascular pathology. RESULTS: Compared to the vascular group, patients with Lewy body disorders exhibited lower perfusion to temporal and occipital lobes than to frontal and parietal lobes (q < 0.05). A greater orthostatic drop in systolic pressure was associated with lower occipito-parietal perfusion in these patients (uncorrected p < 0.005; cluster size ≥ 20 voxels). Although orthostatic hypotension and supine hypertension were strongly correlated (r = -0.79, p < 0.001), the patterns of association for each with perfusion were distinct. Specifically, supine hypertension was associated with high perfusion to anterior and middle cerebral arterial territories, as well as with low perfusion to posterior regions. Perfusion within orthostatic hypotension-defined regions was directly related to performance on visuospatial and attention tasks, independent of dementia severity (p < 0.05). CONCLUSIONS: These findings provide new insight that regional cerebral hypoperfusion is related to orthostatic hypotension, and may be involved in domain-specific cognitive deficits in Lewy body disorders.

Long-term prediction of functional outcome after stroke using the Alberta Stroke Program Early Computed Tomography Score in the subacute stage.

Stroke patients who arrive at hospital more than 24 hours after symptom onset could benefit from a simple means of assessing long-term prognosis in this subacute stage. We evaluated whether clinical factors along with ischemic injury assessed subacutely using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) had predictive value for functional independence after stroke. Computed tomography (CT) scans obtained ≥ 2 days after first-ever ischemic stroke were scored independently and retrospectively by 3 stroke neurologists using the ASPECTS. Functional outcome was measured using the Functional Independence Measure, which assesses the amount of caregiver assistance required by patients during daily activities. Multiple linear regression was used to develop a predictive model for functional prognosis at 1 month, 3 months, and 1 year poststroke. For our 55 patients, CT scanning was done on average 4 days poststroke. The interrater agreement for subacute ASPECTS was excellent, with a κ-weighted value of 0.90. Lesions involving the frontal and superior parietal ASPECTS regions were significant predictors of lower Functional Independence Measure scores at all 3 time points studied. In combination with such factors as age, marital status, and the severity of initial neurologic deficit, a subacute ASPECTS score >5 had significant predictive value for greater functional independence at 3 months (R(2) = 0.701; P < .001) and 1 year (R(2) = 0.528; P < .001) poststroke. Our data indicate that in the subacute stage, ASPECTS is reliable and can help predict which patients may be likely to regain functional independence up to 1 year after sustaining ischemic stroke.

Neurology for internal medicine residents: working towards a national Canadian curriculum consensus.

BACKGROUND: Partly due to the absence of a standardized neurology curriculum, internal medicine residents often perceive neurology lowest in terms of the level of knowledge and clinical confidence. AIMS: To compare the learning needs of internal medicine residents with the perceived learning needs of neurology and internal medicine program directors and to integrate these needs by developing a focused nationwide neurology curriculum for internal medicine residents rotating through neurology. METHODS: Medical residents and neurology and internal medicine program directors from programs across the Canada were asked to complete an online survey and to rank an exhaustive list of neurology topics. A modified Delphi approach was used to obtain consensus on the top 20 topics to include in the curriculum. RESULTS: Over 80% of residents felt their competency in neurology was average or below after completing their neurology rotation. There was very high correlation between the topics ranked by residents and staff. We were able to achieve consensus on 20 topics to be included in a neurology curriculum for internal medicine residents. CONCLUSION: Through a modified Delphi approach we were able to produce a neurology curriculum for internal medicine residents rotating through neurology based on the input of program directors across the country.

Certainty of stroke diagnosis: incremental benefit with CT perfusion over noncontrast CT and CT angiography.

PURPOSE: To systematically evaluate the diagnostic benefits and inter- and intraobserver reliability of an incremental computed tomographic (CT) protocol in the confirmation of clinically suspected stroke, with combined imaging and clinical data as the reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained, and participants gave informed consent. A total of 191 patients (mean age, 67 years +/- 16 [standard deviation]; 105 men) with strokelike symptoms of no more than 3 hours duration were recruited. Blinded review was performed by four readers with limited stroke imaging experience. Diagnostic confidence was recorded on a five-point scale. Logistic regression analysis was used to calculate the difference between the real and observed diagnoses, adjusting for confidence. Predictive effects of observed diagnostic performance and confidence score were quantified with the entropy r(2) value. Sensitivity, specificity, and confidence intervals were calculated while accounting for multiple reader assessments. Receiver operating characteristic (ROC) analyses, including area under the ROC curve, were conducted for three modalities in combination with confidence score. Inter- and intraobserver agreement was established with the Cohen kappa statistic. RESULTS: The final diagnosis was infarct in 64% of the patients, transient ischemic attack in 18%, and stroke mimic in 17%. Large-vessel occlusion occurred in 70% of the patients with an infarct. Sensitivity for stroke determination with noncontrast CT, CT angiography, and CT perfusion increased by 12.4% over that with noncontrast CT and CT angiography and by 18.2% over that with only noncontrast CT for a confidence level of 4 or higher. The incremental protocol was more likely to enable confirmation of clinical stroke diagnosis (odds ratio, 13.3) than was noncontrast CT and CT angiography (odds ratio, 6.4) or noncontrast CT alone (odds ratio, 3.3), The area under the ROC curve was 0.67 for the combination of noncontrast CT and confidence score, 0.72 for the combination of CT angiography and confidence score, and 0.81 for the combination of CT perfusion and confidence score. Inter- and intraobserver agreement increased with progressive sequence use. CONCLUSION: An incremental stroke protocol that includes CT perfusion increases diagnostic performance for stroke diagnosis and inter- and intraobserver agreement.

Crescendo transient Aura attacks: a transient ischemic attack mimic caused by focal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Diagnosis of transient ischemic attack can be difficult because many mimics exist. We report the clinical and neuroimaging features of a distinct hemorrhagic transient ischemic attack mimic. METHODS: Case series. RESULTS: We describe 4 elderly patients presenting with a cluster of stereotyped somatosensory migraine auras, initially referred for "crescendo transient ischemic attacks". Neuroimaging in each patient revealed an unexpected finding of spontaneous focal subarachnoid hemorrhage conforming to a cortical sulcus in the contralateral hemisphere. We postulate that the episodic aura symptoms corresponded to recurrent cortical spreading depression triggered by the presence of subarachnoid blood, and speculate that such episodes could be a presenting feature of cerebral amyloid angiopathy in the absence of typical cerebral microbleeds or history of cognitive impairment. CONCLUSIONS: Focal subarachnoid hemorrhage can present clinically with transient repetitive migraine auras. Awareness of this entity is important because misdiagnosis as cerebral ischemic events could lead to incorrect treatment. We recommend that elderly patients presenting with a cluster of new unexplained migraine auras should be investigated ideally with MRI to detect focal subarachnoid hemorrhage.

Defining the CT angiography 'spot sign' in primary intracerebral hemorrhage.

PURPOSE: The computed tomogram angiography (CTA) 'spot sign' describes foci of intralesional enhancement associated with hematoma expansion in primary intracerebral hemorrhage patients. A consistent radiological definition is required for two proposed recombinant Factor VIIa trials planning patient dichotomization according to 'spot sign' presence or absence. We propose radiological criteria for diagnosis of the CTA 'spot sign' and describe different morphological patterns. MATERIAL AND METHODS: A prospective cohort of 36 consecutive patients presenting with primary intracerebral hemorrhage (ICH) were enrolled in a multicenter collaborative study, and have been included for the present analysis. Three reviewers analyzed the CTA studies in a blinded protocol. Analysis of specific ICH and 'spot sign' features was performed including prevalence, number, size, location, morphology and Hounsfield unit density. RESULTS: Twelve of thirty-six patients (33%) demonstrated a total of 19 enhancing foci consistent with the CTA 'spot sign'. Mean maximal axial 'spot sign' dimension was 3.7 +/- 2.2 mm and mean density was 216 +/- 57.7 HU. No significant differences in age or blood pressure (p = 0.7), glucose (p = 0.9), INR/PTT (p = 0.3 and 0.4) or hematoma location (p = 0.3) were demonstrated between patients with or without the 'spot sign'. Consensus definition and classification criteria for the CTA 'spot sign' are proposed. CONCLUSION: The 'spot sign' is defined as spot-like and/or serpiginous foci of enhancement, within the margin of a parenchymal hematoma without connection to outside vessels. The 'spot sign' is greater than 1.5 mm in maximal dimension and has a Hounsfield unit density at least double that of background hematoma density.

Hemorrhagic transformation of ischemic stroke: prediction with CT perfusion.

PURPOSE: To determine whether admission computed tomography (CT) perfusion-derived permeability-surface area product (PS) maps differ between patients with hemorrhagic acute stroke and those with nonhemorrhagic acute stroke. MATERIALS AND METHODS: This prospective study was institutional review board approved, and all participants gave written informed consent. Forty-one patients who presented with acute stroke within 3 hours after stroke symptom onset underwent two-phase CT perfusion imaging, which enabled PS measurement. Patients were assigned to groups according to whether they had hemorrhage transformation (HT) at follow-up magnetic resonance (MR) imaging and CT and/or whether they received tissue plasminogen activator (TPA) treatment. Clinical, demographic, and CT perfusion variables were compared between the HT and non-HT patient groups. Associations between PS and HT were tested at univariate and multivariate logistic regression analyses and receiver operating characteristic (ROC) analysis. RESULTS: HT developed in 23 (56%) patients. Patients with HT had higher National Institutes of Health Stroke Scale (NIHSS) scores (P = .005), poorer outcomes (P = .001), and a higher likelihood of having received TPA (P = .005) compared with patients without HT. Baseline blood flow (P = .17) and blood volume (P = .11) defects and extent of flow reduction (P = .27) were comparable between the two groups. The mean PS for the HT group, 0.49 mL x min(-1) x (100 g)(-1), was significantly higher than that for the non-HT group, 0.09 mL x min(-1) x (100 g)(-1) (P < .0001). PS (odds ratio, 3.5; 95% confidence interval [CI]: 1.69, 7.06; P = .0007) and size of hypoattenuating area at nonenhanced admission CT (odds ratio, 0.4; 95% CI: 0.2, 0.7; P = .002) were the only independent variables associated with HT at stepwise multivariate analysis. The mean area under the ROC curve was 0.918 (95% CI: 0.828, 1.00). The PS threshold of 0.23 mL x min(-1) x (100 g)(-1) had 77% sensitivity and 94% specificity for detection of HT. CONCLUSION: Admission PS measurement appears promising for distinguishing patients with acute stroke who are likely from those who are not likely to develop HT. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/250/3/867/DC1.