Heit, Jeremy J.

Background: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to early neurological deterioration (END) in this patient population are understudied, but END is known to result in poor functional outcomes. Therefore, we aimed to investigate the factors contributing to END in minor AIS-DMVO cases. Methods: We included patients with AIS-DMVO and minor strokes from 37 sites across North America, Asia, and Europe. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score of ⩽5. The primary outcome measure, END, was defined as a shift of ⩾4 points in the NIHSS score at day one after treatment compared to baseline. Univariable and multivariable logistic regression analyses were performed to identify factors associated with END. Results: Among 559 consecutive patients with DMVO and minor strokes, END was reported in 68 patients. In multivariable analysis, mechanical thrombectomy (MT) was independently associated with higher odds of END (adjusted odds ratio [aOR] 2.37, 95% CI 1.12–5.02, p = 0.02), while intravenous thrombolysis (IVT) was associated with lower odds of END (aOR 0.46, 95% CI 0.26–0.81, p = 0.008). However, the association between MT and END was no longer statistically significant in the IPTW-adjusted analysis (OR 1.65, 95% CI 0.69–3.98, p = 0.26). Hypertension and antiplatelet use at baseline were also independently associated with END. Among MT-treated patients, successful and excellent recanalization and first-pass effect were protective against END. Conclusion: MT was associated with END in patients with minor AIS-DMVO, although this association was not significant after IPTW adjustment. IVT was independently associated with reduced risk of END. These findings support careful patient selection and further study in randomized trials.

Objective Mechanical thrombectomy (MT) is well-established for the treatment of acute ischemic stroke (AIS) from large vessel occlusion (LVO), with growing data supporting the expansion to distal and medium vessel occlusions (DMVO). Despite successful recanalization in DMVO, certain patients still experience poor long-term clinical outcomes, prompting our study to comprehensively explore pre-MT factors influencing outcome despite excellent recanalization (final modified Thrombolysis in Cerebral Infarction [mTICI] score ≥2c). Methods We retrospectively examined data from patients who consecutively underwent MT for a primary middle cerebral artery (MCA) DMVO across 37 centers in North America, Asia, and Europe. We identified baseline clinical and imaging factors associated with poor clinical outcome (defined as a modified Rankin Scale [mRS] score of 3–6) at 3 months, despite excellent recanalization using a multivariable model. Results Between September 2017 and July 2021, 623 patients achieved mTICI > 2b and they were included in our study. Among them, 198 (32%) experienced a poor clinical outcome (mRS 3–6). Predictors of poor clinical outcome included higher age (OR 1.05 [1.03–1.07], p < 0.001), higher NIHSS at admission (OR 1.12 [1.08–1.15], p < 0.001), higher baseline mRS (OR 1.77 [0.96–3.26], p = 0.067), and diabetes (OR 1.59 [1.01–2.48], p = 0.044). Higher ASPECTS was associated with a decreased risk of poor clinical outcome (OR 0.82 [0.71–0.94], p = 0.006). Conclusion Older age, diabetes, higher baseline mRS, and NIHSS were associated with poor clinical outcome in MCA DMVO despite excellent recanalization. Conversely, a higher ASPECTS decreased the probability of such an outcome.

OBJECTIVE Mechanical thrombectomy (MT) is well established for large-vessel occlusion (LVO) strokes, but its safety in distal and medium-vessel occlusions (DMVOs) requires further investigation. This study analyzed the relationship between procedural approaches, petechial hemorrhage (PetH), and clinical outcomes in DMVO thrombectomy, with particular attention to technical considerations and the complex interplay between tissue injury and hemorrhagic complications. METHODS A retrospective cohort study was conducted on DMVO stroke patients treated with MT at 37 stroke centers worldwide from 2016 to 2024. Patients were categorized based on follow-up imaging into those with or without PetH. Four logistic regression models analyzed the association of PetH with favorable functional outcomes (modified Rankin Scale score ≤ 2) at 90 days, early neurological improvement (≥ 4-point National Institutes of Health Stroke Scale score decrease at 24 hours), all-cause mortality, and independent determinants of PetH. Adjusted odds ratios (aORs), 95% confidence intervals, and p values were reported. RESULTS Of 1428 patients, 439 (30.7%) developed PetH. Factors independently associated with PetH were multiple thrombectomy passes (aOR 1.58, 95% CI 1.21–2.06; p = 0.001), IV thrombolysis (aOR 1.31, 95% CI 1.01–1.69; p = 0.04), and the combined use of a stent retriever with aspiration as the first-line method compared with aspiration alone (aOR 1.66, 95% CI 1.15–2.38; p = 0.007). Conversely, general anesthesia (aOR 0.55, 95% CI 0.40–0.77; p < 0.001), higher Alberta Stroke Program Early CT Scores (aOR 0.76, 95% CI 0.69–0.83; p < 0.001), and successful recanalization (aOR 0.56, 95% CI 0.39–0.80; p = 0.002) were significantly associated with a lower odds of PetH. PetH was associated with a decreased odds of favorable functional outcomes (aOR 0.51, 95% CI 0.36–0.73; p < 0.001), reduced early neurological improvement (aOR 0.59, 95% CI 0.44–0.79; p < 0.001), and increased all-cause mortality (aOR 1.84, 95% CI 1.23–2.76; p < 0.001). CONCLUSIONS PetH is a frequent sequela following MT in DMVO strokes and is associated with poorer outcomes, likely reflecting underlying ischemic injury rather than direct causation. Procedural factors influence PetH risk, suggesting medical treatment as first-line therapy for DMVOs, with MT reserved for refractory cases using less aggressive approaches.

Background Endovascular therapy (EVT) for stroke due to distal or medium vessel occlusion (DMVO) is safe. Due to the distinct anatomical characteristics of DMVOs, further evaluation of EVT is crucial to determine which devices may yield better outcomes. Methods A retrospective analysis of adults with DMVO treated in 37 centers (11 countries) was queried. The primary outcome of favorable shift in 90-day modified Rankin Scale (mRS) was compared between patients treated with Trevo versus other devices on first pass using 1:1 propensity score matching (PSM) with multivariable adjustment. Secondary outcomes included the number of pass attempts, final thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), improvement in National Institutes of Health Stroke Scale (NIHSS) at 24h, and 90-day mortality. Results Of the 1115 included patients, 264 (24%) were treated with Trevo (PSM cohort of 261 per group). Trevo use was not associated with a favorable 90-day mRS shift (proportional odds ratio [OR] 1.10, 95% confidence interval [CI] 0.80–1.51). Trevo was associated with fewer passes (adjusted β=-0.25, 95% CI −0.48 - −0.03), higher odds of TICI 2b-3 (adjusted OR 1.97, 95% CI 1.11–3.49), and a greater 24h NIHSS improvement (adjusted β= −1.74, 95% CI −3.11 - −0.36), with no difference in sICH or mortality (p>0.05). Results were similar in sensitivity analyses. Conclusions We observed no safety concerns with Trevo as compared to other EVT devices for DMVO recanalization. There was a signal of better technical efficacy and early clinical improvement.

Background Mechanical thrombectomy (MT) is established as an effective treatment for large vessel occlusion strokes, but its efficacy and safety for medium vessel occlusions (MeVOs) remain less clear. This study examines the impact of periprocedural embolization to a new vascular territory (ENT) on clinical outcomes in patients with MeVO stroke treated with MT. Methods A multicenter, retrospective analysis was conducted using the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry, including 2122 patients with MeVO stroke w­ho underwent MT between September 2017 and July 2023. ENT was defined as filling defects in previously unaffected territories, excluding embolization near the original occlusion, observed on final angiographic runs after retrieval of the primary thrombus. The associations between ENT, procedural variables, and 90-day clinical outcomes were evaluated, including functional independence (modified Rankin Scale (mRS) scores of 0–2), excellent outcomes (mRS 0–1), mortality, and hemorrhagic complications. Results ENT occurred in 2.9% (63/2122) of patients. Longer onset-to-arterial puncture time (adjusted OR 1.03; 95% CI 1.01 to 1.05; P=0.002) and a greater number of passes (adjusted OR 1.15; 95% CI 1.01 to 1.32; P=0.032) were associated with increased ENT risk, while excellent recanalization (thrombolysis in cerebral infarction (TICI) scale score 2c–3) was associated with reduced ENT risk (adjusted OR 0.41; 95% CI 0.23 to 0.72; P=0.002). ENT was not associated with poorer functional independence, mortality, or hemorrhagic complications. Conclusions ENT during MT for MeVO stroke occurs infrequently and does not significantly affect the clinical outcomes. These findings suggest ENT risk should not deter clinicians from performing MT in patients with MeVO. Further prospective studies are needed to validate these results.

Background The hypoperfusion intensity ratio (HIR) has emerged as a vital measure of tissue-level collateral blood flow, helping to identify patients who are likely to benefit from mechanical thrombectomy (MT). We aimed to assess the HIR’s predictive accuracy for clinical outcomes following MT in patients with acute ischemic stroke. Methods PubMed, Embase, and Scopus were searched to identify studies comparing good versus poor HIR groups based on studies’ reported cut-offs. We pooled binary outcomes to calculate odds ratios (OR) and continuous outcomes to calculate mean differences (MD) with 95% confidence intervals (95% CI) using random-effects models. PROSPERO registration code: CRD42024609185. Results 14 studies with 2987 patients, 1553 with good HIR and 1434 with poor HIR, were included in this meta-analysis. Patients with poor HIR exhibited a significantly higher baseline infarct volume compared with those with good HIR (MD 30.6 mL, 95% CI 20.8 mL to 40.3 mL, P<0.01), though baseline National Institutes of Health Stroke Scale (NIHSS) (P=0.12) and Alberta Stroke Program Early CT Score (ASPECTS) (P=0.35) were comparable between groups. The rates of infarct growth (MD 22.4 mL, 95% CI 6.7 mL to 38.0 mL, P<0.01) and 3-month mortality (OR 2.18, 95% CI 1.04 to 4.58, P=0.04) were higher among the poor HIR group and good functional recovery (modified Rankin Scale 0–2 at 3 months) was lower (OR 0.58, 95% CI 0.42 to 0.80, P<0.01). The rates of symptomatic intracranial hemorrhage (P=0.37) and successful reperfusion (P=0.47) were comparable among groups. Conclusion This meta-analysis highlights the significant negative impact of poor HIR on patient outcomes. These findings emphasize the need for personalized treatment strategies for patients with poor HIR.

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT. Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75–100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (modified Rankin Scale (mRS), 0–2). Secondary outcomes included excellent functional outcome at 90 days (mRS, 0–1), mortality, and day 1 post-MT National Institutes of Health Stroke Scale (NIHSS) score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH). Results: Among 1354 patients, 150 were on pre-stroke low-dose aspirin. After applying inverse probability of treatment weighting (IPTW), aspirin use was associated with significantly better functional outcomes (mRS, 0–2: odds ratio (OR) = 1.89, 95% confidence interval (CI) = 1.14 to 3.12) and lower 90-day mortality (OR = 0.56, 95% CI = 0.32 to 1.00). The aspirin group had lower NIHSS scores on day 1 (β = −1.5, 95% CI = −2.8 to −0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI = 0.60 to 1.43). Conclusions: Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.

Background Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown. Methods This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. Only patients with occlusion of the distal branches (M2 and M3) of the middle cerebral artery territory were included. Unsuccessful MT was defined as a modified Thrombolysis in Cerebral Infarction score of 0–2a. Propensity score matching was used to control for confounders. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days after treatment. Multivariable regression analysis was used to assess factors associated with the primary outcome. Results Of 2903 patients screened for eligibility, 532 patients were analyzed (266 per group) after propensity score matching. The MM group had superior functional outcomes, with 32% achieving mRS 0–1 at 90 days compared with 21% in the MT group (P=0.011). Patients in the MM group also had significantly lower rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 16%, P<0.001) and any hemorrhage (18% vs 48%, P<0.001). On multivariable regression, unsuccessful MT was associated with reduced odds of functional independence (OR 0.50, 95% CI 0.29 to 0.85, P=0.011) and increased odds of sICH (OR 4.32, 95% CI 1.84 to 10.10, P<0.001). Mortality rates were similar between groups (27% in MM vs 29% in MT, P=0.73). Conclusion Unsuccessful MT for MeVO was linked to worse outcomes than best MM. These findings highlight the risks of prolonged attempts and emphasize the importance of efficient procedural decision-making to reduce complications and improve patient outcomes.

Background Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.