BACKGROUND: Right to left shunt (RLS), including patent foramen ovale, is a recognized risk factor for stroke. RLS/patent foramen ovale diagnosis is made by transthoracic echocardiography (TTE), which is insensitive, transesophageal echocardiography, which is invasive, and transcranial Doppler (TCD), which is noninvasive and accurate but scarce. METHODS: We conducted a prospective, single-arm device clinical trial of robot-assisted TCD (raTCD) versus TTE for RLS diagnosis at 6 clinical sites in patients who presented with an event suspicious for embolic cerebrovascular ischemia from October 6, 2020 to October 20, 2021. raTCD was performed with standard TCD bubble study technique. TTE bubble study was performed per local standards. The primary outcome was rate of RLS detection by raTCD versus TTE. RESULTS: A total of 154 patients were enrolled, 129 evaluable (intent to scan) and 121 subjects had complete data per protocol. In the intent to scan cohort, mean age was 60±15 years, 47% were women, and all qualifying events were diagnosed as ischemic stroke or transient ischemic attack. raTCD was positive for RLS in 82 subjects (64%) and TTE was positive in 26 (20%; absolute difference 43.4% [95% CI, 35.2%–52.0%]; P <0.001). On prespecified secondary analysis, large RLS was detected by raTCD in 35 subjects (27%) versus 13 (10%) by TTE (absolute difference 17.0% [95% CI, 11.5%–24.5%]; P <0.001). There were no serious adverse events. CONCLUSIONS: raTCD was safe and ≈3 times more likely to diagnose RLS than TTE. TTE completely missed or underdiagnosed two thirds of large shunts diagnosed by raTCD. The raTCD device, used by health professionals with no prior TCD training, may allow providers to achieve the known sensitivity of TCD for RLS and patent foramen ovale detection without the need for an experienced operator to perform the test. Pending confirmatory studies, TCD appears to be the superior screen for RLS compared with TTE (funded by NeuraSignal). REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04604015.

Aims: Evaluate the cost-effectiveness of percutaneous patent foramen ovale (PFO) closure, from a US payer perspective. Lower rates of recurrent ischemic stroke have been documented following percutaneous PFO closure in properly selected patients. Stroke in patients aged <60 years is particularly interesting because this population is typically at peak economic productivity and vulnerable to prolonged disability. Materials and Methods: A Markov model comprising 6 health states (Stable after index stroke, Transient ischemic attack, Post Transient Ischemic Attack, Clinical ischemic stroke, Post clinical ischemic stroke and Death) was constructed to evaluate the cost-effectiveness of PFO closure in combination with medical management versus medical management alone. The base-case model employed a 5-year time-horizon, with transition probabilities, clinical inputs, costs, and utility values ascertained from published and national costing sources. Incremental cost-effectiveness ratio (ICER) was evaluated per US guidelines, utilizing a discount rate of 3.0%. Results: At 5 years, overall costs and quality-adjusted life-years (QALYs) obtained from PFO closure compared with medical management were $16,323 versus $7,670 and 4.18 versus 3.77, respectively. At 5 years, PFO closure achieved an ICER of $21,049 beneficially lower than the conventional threshold of $50,000. PFO closure reached cost-effectiveness at 2.3 years (ICER $47,145). Applying discount rates of 0% and 6% had a negligible impact on base-case model findings. Furthermore, PFO closure was 95.4% likely to be cost-effective with a willingness-to-pay (WTP) threshold of $50,000 and a 5-year time horizon. Limitations: From a cost perspective, our economic model employed a US patient subpopulation, so cost data may not extrapolate to other non-US stroke populations. Conclusion: Percutaneous PFO closure plus medical management represents a cost-effective approach for lowering the risk of recurrent stroke compared with medical management alone.

Introduction: There is an association between cryptogenic strokes and patent foramen ovale (PFO), as well as between migraines with aura and PFO. The purpose of the current study was to compare shunt characteristics in the stroke and migraine populations. Methods: We retrospectively evaluated the degree of the shunt in 68 consecutive patients with cryptogenic stroke (n=33) or migraines with aura (n=35) evaluated in a single transcranial Doppler laboratory. All patients underwent an intravenous injection of agitated saline, followed by the insonation of the middle cerebral artery to determine the degree of the right-to-left shunt. We graded the shunt size according to the number of emboli: Grade I, none; Grade II, 1-10; Grade III, 11-100; and Grade IV, >100. Grades I and II were considered low-grade shunts, and Grades III and IV were considered high-grade. Results: In the 14-month study period, we found 31 high-grade shunts and 37 low-grade shunts. Among migraines with aura patients, 27 (77%) had high-grade shunts, whereas only 4 patients (12%) with cryptogenic stroke had high-grade shunts. These percentages were significantly different between groups (Fisher’s exact test, p<0.0001). Conclusions: In a standardized laboratory using uniform methods, we found a significant difference in shunt size associated with PFO between cryptogenic stroke and migraine with aura patients. We hypothesize that in migraines with aura, venous admixture with arterial blood is the main mechanism by which PFO contributes to the condition. In contrast, cryptogenic strokes associated with PFO are more likely to arise from an atrial septal clot within the PFO space.

Introduction Bedside ultrasound measurement of the optic nerve sheath diameter (ONSD) is emerging as a non-invasive technique to evaluate and predict raised intracranial pressure (ICP) in both children and adults. The prognostic value of increased ONSD on brain computed tomography (CT) scan has previously been correlated with increased intensive care unit (ICU) mortality in patients with severe traumatic brain injury (TBI). Previous studies have also evaluated the association between high-contact sports, such as soccer, and TBI; however, the related changes in ONSD are still unknown. The aim of this study was to evaluate for the natural evolution of changes in ONSD in athletes who participate in high-contact sports. Methods In this prospective observational study, volunteers from a collegiate women's soccer team underwent the measurement of ONSD with transcranial Doppler (TCD). ONSDs were measured during the initial visit during the pre-season period and again at the three-month follow-up. A single experienced neuro-sonographer performed all measurements to eliminate any operator bias. Results Twenty-four female college soccer players between the ages of 18 and 23 were included in this analysis. Mean ONSD during the initial pre-season clinic visit and the three-month follow-up were 4.14 +/- 0.6 mm and 5.02 +/- 0.72 mm, respectively (P < 0.0001). A two-tailed t-test analysis was performed, which resulted in a t-value of 4.76 and P < 0.00001. The average ONSD measured during the post-season follow-up showed a 21.3% increase compared to the baseline. Conclusion The evaluation of high-contact sports athletes is limited due to the lack of objective radiologic and diagnostic tools. Moreover, in an athlete suffering a concussion, return-to-play decisions are heavily dependent on the symptoms reported by the athletes. In our analysis of collegiate women's soccer players, active participation in soccer competitions and practice may be associated with an increase in ONSD, independent of concussions. Further studies are underway to evaluate the clinical significance of these findings as well as possible correlations between concussions and changes in ONSD.