O’Carroll, Cumara B.

Introduction: Despite the recognized linkage between retinal microvascular abnormalities and cerebrovascular ischemic diseases (CVD), the retinal findings’ standardization and the degree of association remain unclear. We aimed to investigate the quantitative association between various retinal microvascular signs and CVD. Hypothesis: retinal microvascular abnormalities best predictive of CVD could be identified by synthesizing estimates of CVD risk from population-based studies. Methods: We followed MOOSE guidelines and systematically searched 6 databases through September 2016 for studies evaluating the association between retinal microvascular abnormalities and white matter hyperintense lesions (WMHI), lacunar infarcts (LI), and cerebral infarctions (CI). Adjusted and unadjusted odds ratios (ORs) and confidence intervals were pooled into the analyses using the DerSimonian and Laird random effects model. Study quality and dissemination biases were assessed and integrated. Results: Thirty-four prospective studies encompassing 84,144 patients were eligible for meta-analysis. After adjustment for vascular risk factors, focal arteriolar narrowing was associated with WMHI (OR, 1.24 [1.01-1.79]), LI (OR, 1.77 [1.14-2.74]), and CI (OR, 1.75 [1.14-2.69]). Venular dilation was significantly associated with LI (OR, 1.46 [1.10-1.93]), whereas retinal hemorrhage was associated with WMHI (OR, 2.23 [1.34-3.70]). Arteriovenous nicking was associated with WMHI (OR, 1.51 [1.22-1.88]) and LI (OR, 1.70 [1.05-2.76]). Any retinopathy exhibited significant association with WMHI, LI, and CI. Heterogeneity was significant ( I 2 >50%) for all syntheses except retinal hemorrhages and WMHI, retinopathy and CI ( I 2 =0.0%) and respectively LI ( I 2 =45.80%). Conclusions: Retinal hemorrhages were most highly associated with WMHI. Focal arteriolar narrowing and retinopathy were associated with WMHI, LI, and CI. Our findings may assist in the development of a noninvasive retinal microvascular tool for routine use in CVD research and clinical practice.

Background: The clinical benefit of patent foramen ovale (PFO) closure in patients with cryptogenic stroke (CS) for recurrent stroke prevention has been a subject of extensive debate. Prior clinical trials failed to show superiority of PFO closure versus medical therapy. Meta-analyses suggested a possible benefit of PFO closure in select patients. Objective: The objective of this study was to critically assess current evidence regarding the efficacy of PFO closure compared with medical therapy for recurrent stroke prevention in patients with CS. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and vascular neurology and interventional cardiology content experts. Results: A randomized, controlled trial was selected for critical appraisal. This trial compared the efficacy of PFO closure and medical therapy in recurrent stroke prevention. A total of 663 patients who had a recent CS attributed to PFO, with a large interatrial shunt or with an associated atrial septal aneurysm were included. No stroke occurred among the 238 patients in the PFO closure group, whereas 14 of the 235 patients in the antiplatelet therapy group had recurrent strokes. Conclusions: Among patients who had a recent CS attributed to PFO with a large interatrial shunt or with an associated atrial septal aneurysm, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone.

Background: Catamenial epilepsy refers to cyclic seizure exacerbation in relation to the menstrual cycle. Three distinct patterns have been described: C1-perimenstrual, C2-periovulatory, and C3-inadequate luteal. There is experimental and clinical evidence that gonadal steroid hormones affect neuronal excitability with estrogens being mainly proconvulsant and progesterone anticonvulsant. If reproductive steroids have a role in seizure occurrence, they may also have a role in treatment. Objective: The objective of this study was to critically assess current evidence regarding the efficacy of progesterone as adjunctive therapy in women with intractable catamenial epilepsy. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and content experts in the fields of epilepsy and gynecology. Results: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the efficacy of adjunctive cyclic natural progesterone therapy versus placebo for seizures in women with intractable partial epilepsy, stratified by catamenial and noncatamenial status. There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation is a significant predictor of the responder rate for progesterone therapy. Conclusions: Cyclic natural progesterone is not superior to placebo in reducing seizure frequency in women with intractable partial epilepsy. Posthoc findings suggest that progesterone may benefit a subset of women with perimenstrually exacerbated seizures.

Background: Adults with cryptogenic stroke often undergo transesophageal echocardiogram (TEE) because this is the gold-standard for evaluation of potential proximal sources of emboli. The risks of performing this invasive test must be weighed against its clinical efficacy and limitations, determined by the rate of positive findings, and the impact on clinical outcome for the patient. Objective: To critically appraise current evidence regarding the rate of positive TEE findings in cryptogenic stroke patients, and analyze the implications of these findings on management decisions and outcomes. Methods: The objective was addressed through the development of a structured, critically appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, and vascular neurology and cardiology content experts. Results: TEE commonly identifies abnormalities, including aorta atherosclerosis in 51%, patent foramen ovale in 43%, and atrial septal aneurysm in 13% of patients. Findings such as left-sided chamber thrombus or intracardiac tumor that definitively warrant a change in management by guideline-supported use of anticoagulation are less common, occurring in ∼3% of patients. Conclusions: TEE identifies potential causal sources of embolus in patients with cryptogenic stroke that leads to changes in management and outcomes at least 3% of the time. Other findings, particularly aorta atherosclerosis, are identified much more commonly but the causal link to stroke is uncertain, thus changes in management in these cases is variable and data describing resulting outcomes are lacking.

Introduction: Major surgery in the past 14 days is a relative contraindication to treatment of acute stroke with intravenous (IV) alteplase. The 2016 American Heart Association/American Stroke Association scientific statement discussing inclusion and exclusion criteria for alteplase in acute stroke allows for provider judgment citing a lack of evidence to support surgery as an absolute contraindication. Case Report: A 59-year-old woman presented with acute left hemiparesis, dysarthria, and acute respiratory failure. National Institutes of Health Stroke Scale was 17. Two days prior she underwent abdominoplasty and liposuction. Computed tomography angiogram of the head demonstrated acute occlusion of right M2, and computed tomography angiogram of the chest was positive for bilateral pulmonary emboli. After urgent consultation with the plastic surgery and neurosurgery teams, the patient was treated with IV alteplase followed by cerebral mechanical thrombectomy. This was complicated by surgical-site hemorrhage in the abdomen requiring operative intervention. Abdominal hemorrhage was controlled and the patient showed remarkable neurological recovery, later being discharged with no residual neurological deficits. Conclusions: Interdisciplinary collaboration can successfully inform the decision to treat acute ischemic stroke with IV alteplase in the setting of recent major surgery.

Antiphospholipid syndrome (APS) encompasses a hypercoagulable state with a markedly increased risk for cerebrovascular complications. In addition to the classic stroke features of APS, however, there are numerous recently described “non-criteria” neurological conditions such as headaches, seizures, and cognitive impairment. We present a case of APS with uncommon neurological manifestations.

Background: Central retinal artery occlusion (CRAO) is a neurological and ophthalmologic emergency associated with poor visual recovery. There is a dilemma regarding the appropriate treatment, as formal guidelines are lacking. Despite being considered an ocular equivalent of cerebral infarction, the time window of intravenous (IV) thrombolysis administration for maximum efficacy and safety in CRAO remains uncertain. Objective: To critically assess the current evidence regarding the safety and effectiveness of IV thrombolysis in the treatment of patients with CRAO. Methods: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of vascular neurology and ophthalmology. Results: A recent patient-level meta-analysis was selected for critical appraisal. The study compared the visual recovery rates after IV thrombolysis in CRAO against the natural history of this illness and conservative therapies (ocular massage, anterior chamber paracentesis, and/or hemodilution). Time to thrombolytic therapy administration had a significant impact on visual recovery in CRAO (P<0.001). IV thrombolysis within the first 4.5 hours after symptom onset resulted in recovery of vision in 50.0% of the patients [95% confidence interval (CI), 32.4%-67.6%]. The rate of visual recovery was nearly 3 times higher than in the natural history cohort [odds ratio, 4.7 (95% CI, 2.3-9.6); P<0.001], with a 32.3% absolute risk reduction and a number needed to treat of 4.0 (95% CI, 2.6-6.6). There was no significant difference in the recovery rate after thrombolysis compared with the natural history cohort for those patients treated after 4.5 hours. No major hemorrhages occurred after alteplase administration in this meta-analysis. Conclusions: IV thrombolysis in CRAO seems to be safe and effective within the first 4.5 hours of symptom onset. A clinical decision based on this meta-analysis alone cannot be made due to several limitations. A randomized controlled clinical trial of early IV alteplase administration in CRAO is necessary to provide evidence-based therapeutic guidance.

Intravenous recombinant tissue plasminogen activator continues to be first-line therapy for patients with acute ischemic stroke presenting within the appropriate time window, but one potential limitation is the low rate of recanalization in the setting of large artery occlusions. Intra-arterial (IA) treatment is effective for emergency revascularization of proximal intracranial arterial occlusions, but proof of benefit has been lacking until recently. Our goal is to outline the history of endovascular therapy and review both IA thrombolysis and mechanical interventions. In addition, we will discuss the impact of important trials such as the Third Interventional Management of Stroke (IMS3) trial, and the more recent trials Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) on acute stroke management and the implications for the practicing neurohospitalist.