Nirav Bhatt

IV thrombolysis (IVT) is the standard-of-care evidence-based treatment of eligible patients with acute ischemic stroke (AIS) within 4.5 hours of symptom onset. Emerging evidence supports its use beyond this time window, leading to expanded recommendations for selected patients presenting between 4.5 and 24 hours. We performed a systematic review and meta-analysis to evaluate IVT in the 4.5- to 24-hour window and to explore sources of between-study heterogeneity. We searched MEDLINE, Cochrane Library, and ClinicalTrials.gov from inception through February 2026. Eligible studies were randomized controlled trials (RCTs) or individual patient-data meta-analyses of RCTs comparing IVT with control in patients with AIS presenting beyond 4.5 hours from last known well. The primary outcome was excellent functional recovery, defined as a modified Rankin Scale (mRS) of 0-1 at 90 days. Secondary outcomes included functional independence (mRS of 0-2 at 90 days); change in mRS disability, quantified as the common odds ratio (OR) for a 1-point improvement across the full ordinal mRS distribution (ordinal analysis); and safety measures such as 90-day mortality and symptomatic intracranial hemorrhage (sICH). Risk ratios (RRs) with 95% CIs were pooled. Multivariable meta-regression simultaneously modeled thrombolytic agent, endovascular thrombectomy context, and territory to disentangle confounded predictors. Fifteen studies representing 18 RCTs and encompassing 5,168 patients were included in the primary analysis. Of the 18 included RCTs, 11 required advanced perfusion imaging (CTP or MRP mismatch) or diffusion-weighted imaging/fluid-attenuated inversion recovery mismatch to confirm salvageable tissue; the remaining 7 permitted noncontrast CT/CT angiography-based selection. IVT significantly improved excellent functional outcome at 90 days (mRS 0-1; 40.3% vs 33.2%, RR 1.21; 95% CI 1.13-1.30; p < 0.001; number needed to treat [NNT] = 14) and good functional outcome (mRS 0-2; 54.5% vs 50.1%, RR 1.09; 95% CI 1.04-1.15; p < 0.001; NNT = 23). IVT was associated with significantly greater odds of reduced disability across the full mRS spectrum (common OR 1.18; 95% CI 1.07-1.32; p = 0.004). IVT increased the risk of sICH (3.2% vs 1.4%; RR 1.90; 95% CI 1.28-2.84; p = 0.002; number needed to harm = 57) but did not increase 90-day mortality (13.7% vs 13.0% RR 1.04; 95% CI 0.92-1.18; p = 0.53). Meta-regression showed that thrombectomy (β = -0.275, p = 0.012 for mRS shift; β = -0.186, p = 0.032 for mRS 0-2) is the primary driver of between-study heterogeneity, explaining 66%-100% of intertrial variance. Extended-window IVT improves functional outcomes across a wider spectrum of stroke subgroups than previously recognized. The benefit seems greatest for patients with more severe strokes in settings where thrombectomy is unavailable, providing the evidence base for offering a critical reperfusion strategy for the substantial proportion of patients worldwide who lack timely access to thrombectomy. This study provides American Academy of Neurology Class I evidence that IVT administered 4.5-24 hours after moderate-to-severe AIS onset in patients with salvageable tissue, where thrombectomy is not readily available, improves functional outcome at 90 days without increasing mortality.

Intravenous thrombolysis (IVT) has been the mainstay of acute ischemic stroke (AIS) treatment for over three decades. Recently, several studies have evaluated the safety and efficacy of IVT in certain complex clinical scenarios such as bridging IVT with mechanical thrombectomy (MT) versus direct MT, MT in distal medium vessel occlusions (DMVOs), and extended time window reperfusion. Many of these scenarios overlap with neurointerventional treatment strategies. This updated evidence has uncovered certain nuances in AIS treatment (transfer vs non-transfer patients, degree of disability, feasibility of MT) that warrant consideration in medical decision-making in addition to the conventional risks-versus-benefits discussion. Furthermore, as an increasing number of neurologists with diverse subspecialty interests are involved in AIS triage and treatment decision-making across various patient-care models (telestroke, spoke and hub systems, etc), variability in data interpretation may lead to inconsistencies in the administration of these time-sensitive therapies. In this vignette-based narrative review, we focus on evolving ‘gray zones’ of AIS reperfusion therapy that are particularly relevant to neurointerventional practice: (1) bridging IVT before MT, and (2) reperfusion strategies for DMVOs, with the role of IVT in the extended time window primarily discussed within the second vignette and, to a lesser extent, in the first. This paper is not meant to be a treatment guideline but rather a case-based exercise to provide a better understanding of the new data in this area.

Background: In the United States, the impact of bypassing the nearest local stroke center to facilitate direct transport of nonurban patients to a thrombectomy‐capable center (TCC) for mechanical thrombectomy (MT) remains unclear. We compared intravenous thrombolysis and MT treatment times between patients transferred directly to a TCC and those transported initially to a local stroke center and undergoing MT. Methods: In this retrospective observational study within an academic health care system with integrated telestroke and transport services, we included consecutive nonurban patients (ground transport ≥15 minutes to TCC) who were transported via emergency medical services and underwent MT between January 2021 and October 2024. Patients were categorized into those transported directly to TCC or those initially taken to 1 of 12 telestroke‐supported local stroke centers and subsequently transferred to TCC. These groups were compared using inverse probability of treatment weighting. Outcomes included first medical contact–to–intravenous thrombolysis, first medical contact–to–arterial puncture, and first medical contact–to–arrival times, among others. All times are expressed as median (IQR). Results: Among 304 patients (transported directly to TCC, 174; initial transport to local stroke center, 130; median age, 72 [IQR, 62–82] years; median National Institutes of Health Stroke Scale score, 16 [IQR, 12–22]; 36.5% air transported), first medical contact–to–intravenous thrombolysis (75 [IQR, 65–89] versus 86 [IQR, 72–110] minutes; P P P P P <0.001) times. Conclusions: Among nonurban patients undergoing MT, direct transport to a TCC accelerated treatment times and may improve clinical outcomes. Our study highlights inefficiencies in regional systems of care.

The therapeutic efficacy and safety of IV thrombolysis (IVT) for patients with minor strokes remain a subject of significant debate and uncertainty. This meta-analysis aimed to assess the comparative effectiveness and safety of IVT vs nonthrombolytic standard of care (NT-SC) in minor strokes, focusing exclusively on data from randomized controlled trials (RCTs). A comprehensive literature search was conducted to identify RCTs evaluating IVT in minor stroke, defined as a NIH Stroke Scale (NIHSS) score ≤5. The primary outcome was excellent functional recovery, defined as a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary outcomes included functional independence (mRS 0-2 at 90 days) and safety end points, including 90-day mortality, recurrent stroke, symptomatic intracranial hemorrhage (sICH), and any ICH. The study was registered with PROSPERO (CRD42024621714). The primary analysis included data from 4 RCTs that exclusively enrolled patients with minor stroke (N = 3,364; age range: 56-80 years). Secondary analyses incorporated post hoc and subgroup data on patients with minor stroke from earlier RCTs. In the primary analysis, IVT was not significantly associated with higher odds of excellent functional recovery at 90 days compared with NT-SC (mRS 0-1; odds ratio [OR] 0.85, 95% CI 0.70-1.03). IVT was significantly associated with lower odds of achieving 90-day functional independence (mRS 0-2; OR 0.71, 95% CI 0.55-0.91) and higher odds of both sICH (OR 5.22, 95% CI 1.76-15.48) and 90-day mortality (OR 2.40, 95% CI 1.23-4.67) compared with NT-SC. Subgroup analysis showed a nonsignificant association of IVT with odds of excellent functional recovery across both groups with disabling symptoms (OR 0.84, 95% CI 0.38-1.88) and nondisabling symptoms (OR 0.82, 95% CI 0.66-1.03). The pooled analysis, which incorporated nonoverlapping subgroups and post hoc data, yielded consistent findings. The findings suggest that IVT does not confer improved functional outcomes among patients with minor strokes and can be associated with higher odds of sICH and mortality at 90 days compared with NT-SC. Since most of the included patients presented with nondisabling minor strokes, additional studies on patients with mildly disabling symptoms are warranted.

Background This study evaluated the performance of the newer-generation Emboguard Balloon Guide Catheter (EBGC) in treating anterior circulation large vessel occlusions (LVOs). Methods A prospectively maintained endovascular thrombectomy database was reviewed to identify consecutive non-tandem LVO patients treated with the EBGC. Procedural outcomes included rates of complete recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3), successful recanalization (mTICI 2b/3), first-pass effect (FPE) (mTICI 2c/3 after the first pass), modified FPE (mTICI 2b/3 after the first pass), and the number of passes. Clinical outcomes assessed included National Institutes of Health Stroke Scale (NIHSS) scores at discharge, functional independence (modified Rankin Scale (mRS) 0–2), and fair outcomes (mRS 0–3). Safety outcomes evaluated included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. Results Of the 72 patients included, 56.9% (41/72) were female, with a median age of 73 years (IQR 67–83). Most patients presented with middle cerebral artery (MCA) occlusions (M1 in 59.7% (43/72) and dominant/co-dominant M2 in 25.0% (18/72)). Successful recanalization (mTICI 2b/3) was achieved in 98.6% (71/72) of cases, and complete recanalization (mTICI 2c/3) was achieved in 76.4% (55/72), with a median of 1 pass (IQR 1–2). FPE and modified FPE were achieved in 48.6% (35/72) and 56.9% (41/72) of cases, respectively. The median NIHSS improved significantly from 17 (IQR 11–21) at baseline to 4 (IQR 1–12) at discharge. sICH occurred in only 1.4% (1/72) of cases. At 90 days, 42.6% (23/54) of patients achieved functional independence (mRS 0–2), and mRS 0–3 in 63.2% (36/57). Conclusions The EBGC demonstrated promising potential with high rates of FPE and successful recanalization together with clinical improvements and a favorable safety profile.

Background We sought to identify systemic factors influencing door-to-puncture times (DTP) among patients with pre-arrival notifications presenting directly to a comprehensive stroke center (CSC) and undergoing emergent mechanical thrombectomy (MT). Methods In this retrospective analysis of a prospectively maintained registry of acute ischemic stroke (AIS) patients undergoing MT at two CSCs between January 2021 and October 2023, we included consecutive AIS patients presenting directly to the CSC with pre-arrival notifications via emergency medical services (EMS) and who underwent emergent MT. We excluded patients with known confounders to DTP and divided this cohort into two groups: DTP ≤75 min and >75 min. We used variables with P value 75 min, adjusting for door-to-CT time. Results Of 900 patients, 605 were inter-facility transfers, 89 were excluded due to known confounders/missing prehospital notifications, leaving 206 qualifying patients. On multivariable analysis, not meeting American Heart Association (AHA) level 1 criteria (adjusted OR (aOR) 3.04, 95% CI 1.62 to 5.82, P75 min DTP times. Most patients (62.3%) had no clearly documented reasons for delay in MT, whereas 25.8% of delays were attributed to prolonged medical decision-making. Conclusion Arrival outside business hours, not meeting AHA level 1 criteria, and lack of PSSS acquisition by EMS were associated with prolonged DTP. Impacting modifiable factors such as prehospital assessment of stroke severity is an optimal target for quality improvement.

Background Carotid web (CaW) is a subtype of fibromuscular dysplasia that predominantly involves the intimal layer of the arterial wall and is commonly overlooked as a separate causative entity for recurrent strokes. CaW is defined as a shelf-like lesion at the carotid bulb, although different morphological features have been reported. Optical coherence tomography (OCT) has been described in the literature as a useful microscopic and cross-sectional tomographic imaging tool. This study aimed to evaluate the potential utility of OCT in characterizing the wall structure features of patients with suspected CaW. Methods Retrospective analysis of patients with suspected CaW who underwent digital subtraction angiography (DSA) coupled with OCT of the carotid bulb from 2018 to 2021 in a single comprehensive stroke center. Results Sixteen patients were included. The median age was 56 years (IQR 46–61) and 50% were women. OCT corroborated the diagnosis of CaW in 12/16 (75%) cases and ruled it out in 4/16 (25%) patients in whom atherosclerotic disease was demonstrated. Five of the 12 lesions demonstrated a thick fibrotic ridge consistent with CaW but also showed atherosclerotic changes in the vicinity of the carotid bulb (labeled as “CaW+”). In 4/16 (25%) patients, microthrombi adhered to the vessel wall were noted on OCT (inside the CaW pocket or just distal to the web), none of which were observed on CT angiography or DSA. Conclusions OCT may have value as a complementary imaging tool in the investigation of patients with suspected CaW and atypical morphological features. Further studies are warranted.