Abstract - Donanemab in Early Alzheimer’s Disease: Greater Benefit in Lower Tau Burden (P2-12.011)

Title: Donanemab in Early Alzheimer’s Disease: Greater Benefit in Lower Tau Burden (P2-12.011)

Authors: Aswathi Sajeendran, Jamir Pitton Rissardo, Omar Elmandouh, and Ana Leticia Fornari Caprara

Conference: 2026 AAN, Chicago, IL

Objective

To evaluate the effect of donanemab compared to placebo on cognitive and functional outcomes in Alzheimer’s disease (AD) patients stratified by tau burden (low/medium [L/M] vs. high [H]).

Background

Donanemab, an anti-amyloid monoclonal antibody, has shown promise in slowing cognitive decline in early AD. Tau pathology may influence treatment response, but subgroup effects remain unclear.

Design/Methods

We systematically reviewed placebo-controlled trials of donanemab in AD reporting outcomes by tau burden. Standardized mean differences (SMD) with 95% confidence intervals (CI) were pooled using inverse-variance methods under fixed- and random-effects models. Outcomes included the integrated Alzheimer’s Disease Rating Scale (iADRS), Clinical Dementia Rating–Sum of Boxes (CDR-SB), ADAS-Cog13, ADCS-iADL, and MMSE. The between-study variance was estimated using REML, and SMDs were calculated as Hedges’ g.

Results

Donanemab significantly improved iADRS (g = 3.28; 95% CI 2.09–4.48; p < 0.01) and favored treatment on CDR-SB (g = –0.61; 95% CI –0.82 to –0.40), ADAS-Cog13 (g = –1.54; 95% CI –2.21 to –0.86), ADCS-iADL (g = 1.70; 95% CI 0.93–2.47), and MMSE (g = 0.53; 95% CI 0.18–0.89). Subgroup analysis showed greater benefit in L/M tau versus H tau across most outcomes: iADRS (L/M: g = 3.80; 95% CI 2.37–5.23; H: g = 0.94; 95% CI –2.16 to 4.04), CDR-SB (L/M: g = –0.67; 95% CI –0.94 to –0.40; H: g = –0.69; 95% CI –1.18 to –0.20), ADAS-Cog13 (L/M: g = –1.72; 95% CI –2.52 to –0.92; H: g = –0.40; 95% CI –2.11 to 1.31), ADCS-iADL (L/M: g = 2.00; 95% CI 1.06–2.94; H: g = 0.99; 95% CI –0.81 to 2.79), and MMSE (L/M: g = 0.57; 95% CI 0.14–1.00; H: g = 0.33; 95% CI –0.47 to 1.13). Between-group differences were not statistically significant (p > 0.25). Heterogeneity was low (I² ≤ 26%).

Conclusions

Donanemab demonstrates clinically meaningful benefits in early AD, particularly among patients with lower tau burden. While high-tau patients showed attenuated responses, subgroup differences were not statistically significant, warranting further investigation.

Citation

Sajeendran A, Rissardo JP, Elmandouh O, Caprara AL. Donanemab in Early Alzheimer’s Disease: Greater Benefit in Lower Tau Burden (P2-12.011). Neurology 2026;106(11_suppl_1):868. doi: 10.1212/WNL.0000000000213161.

Figure 1. Forest plot of iADRS showing significant benefit of donanemab, with greater effect in low/intermediate tau burden and attenuated response in high tau patients.

Figure 2. Forest plot of CDR-SB demonstrating improved clinical progression with donanemab, consistent across tau strata with low heterogeneity.

Figure 3. Forest plot of ADAS-Cog13 showing cognitive improvement favoring donanemab, with stronger effects in low/medium tau and attenuated benefit in high tau.

Abstract - Do SGLT2 Inhibitors Influence Parkinson’s Disease Risk? A Meta-analysis of Randomized Trials (P6-17.012)

Title: Do SGLT2 Inhibitors Influence Parkinson’s Disease Risk? A Meta-analysis of Randomized Trials (P6-17.012)

Authors: Theres Boby Alexander, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, and Ian M. Walker

Conference: 2026 AAN, Chicago, IL

Objective

To evaluate whether sodium-glucose cotransporter-2 (SGLT2) inhibitors influence the risk of Parkinson’s disease (PD) in patients with diabetes, heart failure, or chronic kidney disease.

Background

SGLT2 inhibitors have transformed the management of type 2 diabetes and heart failure by reducing cardiovascular events and slowing kidney disease progression. Preclinical studies suggest neuroprotective effects. Given shared metabolic and inflammatory pathways between diabetes and PD, SGLT2 inhibitors may influence PD risk.

Design/Methods

A systematic search of ClinicalTrials.gov identified randomized controlled trials reporting PD incidence in SGLT2 inhibitor versus placebo arms. No eligible data were found for ertugliflozin, enavogliflozin, henagliflozin, ipragliflozin, luseogliflozin, or tofogliflozin. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects Mantel-Haenszel model, and heterogeneity was assessed with the I² statistic.

Results

Fourteen trial arms from 12 unique studies (n ≈ 64,000; follow-up 7–50 months) were included. Two arms were excluded from pooled analysis due to zero events in both groups. The pooled OR for PD was 0.55 (95% CI: 0.27–1.12; p = 0.20). Heterogeneity was negligible (I² = 0%), and the prediction interval ranged from 0.23 to 1.50. Subgroup analyses showed no significant effect for individual agents: empagliflozin 10 mg (OR 0.64, 95% CI 0.17–2.43), empagliflozin 25 mg (OR 0.33, 95% CI 0.01–8.15), dapagliflozin 10 mg (OR 0.33, 95% CI 0.09–1.23), sotagliflozin (OR 0.25, 95% CI 0.03–2.24), canagliflozin 100 mg (OR 3.00, 95% CI 0.31–28.81), and bexagliflozin (OR 1.50, 95% CI 0.06–36.99). No evidence of publication bias was detected (Egger’s p = 0.96).

Conclusions

SGLT2 inhibitors do not significantly alter the risk of PD. These findings support their neurological safety, though longer follow-up and dedicated neurodegenerative outcome trials are warranted.

Citation

Alexander TB, Rissardo JP, Caprara AL, Walker IM. Do SGLT2 Inhibitors Influence Parkinson’s Disease Risk? A Meta-analysis of Randomized Trials (P6-17.012). Neurology 2026;106(11_suppl_1):862. doi: 10.1212/WNL.0000000000213157.

Figure 1. Forest plot of randomized trials evaluating SGLT2 inhibitors and Parkinson’s disease risk, showing no significant association (OR 0.55; 95% CI 0.27–1.12) with negligible heterogeneity.

Abstract - Responsive Neurostimulation Targeting Thalamic Nuclei in Lennox-Gastaut Syndrome: A Systematic Review of Clinical Outcomes and Programming Parameters (P1-10.002)

Title: Responsive Neurostimulation Targeting Thalamic Nuclei in Lennox-Gastaut Syndrome: A Systematic Review of Clinical Outcomes and Programming Parameters (P1-10.002)

Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Salman Assad, Evren Burakgazi-Dalkilic, and Eric P. Nagele

Conference: 2026 AAN, Chicago, IL

Objective

To summarize clinical outcomes, stimulation parameters, and safety of thalamic responsive neurostimulation (RNS) in patients with Lennox-Gastaut syndrome (LGS).

Background

LGS is a severe developmental and epileptic encephalopathy often refractory to medications and vagus nerve stimulation. Deep brain stimulation of the centromedian (CM) nucleus has shown promise, but data on closed-loop RNS targeting thalamic nuclei remain limited. Understanding programming strategies and outcomes is critical for optimizing therapy.

Design/Methods

We performed a structured review of PubMed and clinical trial registries through September 2025 for studies reporting RNS in LGS or LGS phenotype. Extracted variables included demographics, seizure outcomes (≥50% responder rate), stimulation parameters, lead configuration, follow-up duration, and adverse events.

Results

Nine studies (n=30 LGS patients) were identified: 2 case reports, 4 case series, 1 multicenter cohort, and 2 feasibility trials. Mean age at implant ranged from 12–17 years; follow-up ranged 5–24 months. Targets included CM (most common), anterior nucleus, and pulvinar. Reported programming typically used high-frequency stimulation (100–200 Hz), pulse width 160 μs, and current 1–3 mA, with individualized titration. ≥50% responder rates varied widely across studies (0%–100%), with a pooled weighted estimate of 56.7% (95% CI: 38.9%–74.4%). Adverse events were rare; one case of myasthenia gravis and two infections requiring intervention were reported. Concurrent neuromodulation (e.g., active VNS) was feasible without device interference. Ongoing IDE trials (NCT05339126) aim to clarify long-term efficacy and biomarker-driven programming.

Conclusions

Thalamic RNS is a promising adjunctive therapy for LGS, offering individualized, closed-loop modulation with favorable safety. Early evidence suggests clinically meaningful seizure reduction in most patients, though heterogeneity in targets and programming underscores the need for prospective trials and standardized protocols.

Citation

Caprara AL, Rissardo JP, Assad S, Burakgazi-Dalkilic E, Nagele EP. Responsive Neurostimulation Targeting Thalamic Nuclei in Lennox-Gastaut Syndrome: A Systematic Review of Clinical Outcomes and Programming Parameters (P1-10.002). Neurology 2026;106(11_suppl_1):689. doi: 10.1212/WNL.0000000000213061.

Figure 1. Summary of included studies on thalamic responsive neurostimulation in Lennox–Gastaut syndrome, detailing targets, stimulation parameters, responder rates, and safety outcomes across reported cohorts.

Abstract - To Anticoagulate or Not? Stroke Prevention in Atrial Fibrillation Patients with a Single Additional Stroke Risk Factor (P3-5.001)

Title: To Anticoagulate or Not? Stroke Prevention in Atrial Fibrillation Patients with a Single Additional Stroke Risk Factor (P3-5.001)

Authors: Arthur Gribachov, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, and Vishnu Vardhan Byroju

Conference: 2026 AAN, Chicago, IL

Objective

To compare ischemic stroke (IS) risk between oral anticoagulant (OAC) and no-OAC, and new-oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with a non-sex-related CHA2DS2-VASc score of 1.

Background

The benefit of OAC in AF patients with a single additional stroke risk factor remains uncertain. Evidence comparing NOACs and VKAs in this intermediate-risk group is limited.

Design/Methods

A systematic PubMed search identified studies evaluating stroke prevention in this population. A meta-analysis of four observational studies (six arms) was performed using Mantel-Haenszel methods. Odds ratios with 95% confidence intervals were pooled under fixed- and random-effects models. Tau estimator: DerSimonian-Laird. Heterogeneity was assessed with I² and Cochran’s Q. Publication bias was evaluated using trim-and-fill and fail-safe N. Subgroup analyses were stratified by follow-up duration.

Results

For OAC versus no-OAC, fixed-effect analysis showed a significant reduction in IS risk (OR 0.78; 95% CI 0.69 to 0.87; p < 0.01), whereas random-effects analysis was nonsignificant (OR 0.82; 95% CI 0.62 to 1.09). Subgroup estimates favored OAC at 1.5-year follow-up (OR 0.69) and 2.5-year follow-up (OR 0.74). For NOAC versus VKA, both fixed-effect and random-effect analyses were non-significant, with similar findings at 1-year (OR 0.50; 95% CI 0.19–1.33) and 2-year (OR 0.65; 95% CI 0.30–1.38) follow-up. Heterogeneity was low for OAC versus no OAC (I² = 1%) but moderate for NOAC versus VKA (I² = 36%).

Conclusions

In AF patients with a single additional stroke risk factor, OAC may reduce IS risk compared with no-OAC, particularly with longer follow-up. NOACs and VKAs appear similarly effective in this population.

Citation

Gribachov A, Rissardo JP, Caprara AL, Byroju VV. To Anticoagulate or Not? Stroke Prevention in Atrial Fibrillation Patients with a Single Additional Stroke Risk Factor (P3-5.001). Neurology 2026;106(11_suppl_1):943. doi: 10.1212/WNL.0000000000213209.

Figure 1. Forest plot comparing oral anticoagulation strategies in atrial fibrillation with CHA₂DS₂-VASc = 1, showing reduced stroke risk with OAC versus no-OAC and no difference between NOACs and VKAs.

Abstract - Virtual Reality Meets Reality: Wii-based Rehabilitation Shows Comparable Effects in Parkinson’s Disease (P6-17.007)

Title: Virtual Reality Meets Reality: Wii-based Rehabilitation Shows Comparable Effects in Parkinson’s Disease (P6-17.007)

Authors: Omar Elmandouh, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, and Ian M. Walker

Conference: 2026 AAN, Chicago, IL

Objective

To evaluate the clinical impact of Wii-based interventions on balance, mobility, gait, and quality of life in individuals with Parkinson’s disease.

Background

Conventional physical therapy remains the cornerstone of rehabilitation in PD, but adherence can be limited by monotony and accessibility barriers. Exergaming platforms, such as the Nintendo Wii, offer an interactive and attractive alternative by combining physical exercise with real-time visual feedback. These systems aim to enhance motor learning and neuroplasticity through task-specific, repetitive practice in a stimulating environment. However, the clinical effectiveness of Wii- based interventions compared to standard therapy remains uncertain, warranting systematic evaluation.

Design/Methods

A meta-analysis of randomized controlled trials comparing Wii-based interventions to conventional therapy. Outcomes included Berg Balance Scale (BBS), 10-Meter Walk Test (10-MWT), Timed Up and Go (TUG), Dynamic Gait Index (DGI), and Parkinson’s Disease Questionnaire-39 (PDQ-39). Pooled estimates were calculated using random-effects models and expressed as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI).

Results

Seven trials were included. Wii-based therapy showed no significant advantage over conventional therapy for balance (BBS MD −0.06; 95% CI −1.49 to 1.37; I²=0%) or gait speed (10-MWT SMD −0.22; 95% CI −0.64 to 0.20; I²=0%). Mobility improvements were small and not statistically significant (TUG SMD −0.12; 95% CI −0.36 to 0.13; I²=36%). Gait adaptability showed a non-significant trend favoring control (DGI MD −0.65; 95% CI −1.71 to 0.40; I²=55%). Quality of life changes were minimal (PDQ-39 MD −1.71; 95% CI −5.34 to 1.92; I²=0%). Overall, Wii-based interventions were comparable to conventional therapy across all outcomes, with low to moderate heterogeneity.

Conclusions

Wii-based rehabilitation offers similar benefits to conventional therapy for balance, mobility, and quality of life in Parkinson’s disease. While not superior, its engaging nature may enhance adherence, supporting its role as an alternative or adjunct in rehabilitation programs.

Citation

Elmandouh O, Rissardo JP, Caprara AL, Walker IM. Virtual Reality Meets Reality: Wii-based Rehabilitation Shows Comparable Effects in Parkinson’s Disease (P6-17.007). Neurology 2026;106(11_suppl_1):622. doi: 10.1212/WNL.0000000000213023.

Figure 1. Forest plot of Berg Balance Scale showing no difference between Wii-based and conventional therapy in Parkinson’s disease (MD −0.06; 95% CI −1.49 to 1.37).

Figure 2. Forest plot of 10-Meter Walk Test showing no significant difference in gait speed between Wii-based and conventional therapy (SMD −0.22; 95% CI −0.64 to 0.20).

Figure 3. Forest plot of Timed Up and Go demonstrating small, non-significant mobility differences between Wii-based and conventional therapy (SMD −0.12; 95% CI −0.36 to 0.13).

Abstract - Inverse Association Between Parkinson’s Disease and Rheumatoid Arthritis: A Meta-analysis of Observational Studies (P11-17.004)

Title: Inverse Association Between Parkinson’s Disease and Rheumatoid Arthritis: A Meta-analysis of Observational Studies (P11-17.004)

Authors: Theres Boby Alexander, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, and Ian M. Walker

Conference: 2026 AAN, Chicago, IL

Objective

To evaluate the association between Parkinson’s disease (PD) and rheumatoid arthritis (RA) using a systematic meta-analysis of observational studies.

Background

PD and RA are chronic disorders with distinct clinical phenotypes but overlapping immunological and inflammatory pathways. Clarifying this relationship is critical for understanding shared pathophysiology and identifying potential therapeutic targets.

Design/Methods

We systematically searched PubMed and Embase for observational studies reporting RA incidence in PD patients (PD→RA) or PD incidence in RA patients (RA→PD). Twelve studies met inclusion criteria (4 PD→RA; 8 RA→PD). Data were pooled using a binary outcome meta-analysis with the Mantel-Haenszel method under a random-effects model (DerSimonian-Laird estimator). Risk ratios (RR) with 95% confidence intervals (CI) were calculated. Between-study heterogeneity was assessed using τ², I², and Cochran’s Q test. Publication bias was evaluated using Egger’s regression, Begg’s rank correlation, and trim-and-fill analysis.

Results

The overall random-effects model showed no significant association (RR 0.99; 95% CI: 0.77 to 1.28; p = 0.95), with high heterogeneity (τ² = 0.15; I² = 95%). Subgroup analysis revealed non-significant association with PD and risk of RA (RR = 0.81; 95% CI: 0.48–1.35), as well as the association with RA and risk of PD (RR = 1.09; 95% CI: 0.79–1.50). Publication bias tests were non-significant (Egger’s p = 0.68; Begg’s p = 0.58), although trim-and-fill suggested one potentially missing study.

Conclusions

PD was not associated with RA risk, and RA was not linked to PD risk. Further studies are needed to elucidate possible association between RA and PD.

Citation

Alexander TB, Rissardo JP, Caprara AL, Walker IM. Inverse Association Between Parkinson’s Disease and Rheumatoid Arthritis: A Meta-analysis of Observational Studies (P11-17.004). Neurology 2026;106(11_suppl_1):861. doi: 10.1212/WNL.0000000000213156.

Figure 1. Forest plot of observational studies assessing bidirectional associations between Parkinson’s disease and rheumatoid arthritis, showing no significant overall relationship and substantial interstudy heterogeneity across subgroups.

Abstract - Daytime Napping and Ischemic Stroke Risk: Evidence from a Meta-analysis (P2-5.014)

Title: Daytime Napping and Ischemic Stroke Risk: Evidence from a Meta-analysis (P2-5.014)

Authors: Vishnu Vardhan Byroju, Jamir Pitton Rissardo, and Ana Leticia Fornari Caprara

Conference: 2026 AAN, Chicago, IL

Objective

To evaluate whether daytime napping is associated with an increased risk of ischemic stroke.

Background

Daytime napping is a common behavior globally, yet its impact on cerebrovascular outcomes remains uncertain. While some studies suggest restorative benefits, others raise concerns about increased vascular risk. Clarifying this association is important for public health recommendations.

Design/Methods

A systematic search of PubMed was conducted using the terms “ischemic stroke” and “nap.”We included observational studies comparing the incidence of ischemic stroke between habitual nappers and non-nappers. Odds ratios (OR) with 95% confidence intervals (CI) were pooled using a random-effects model with the restricted maximum likelihood (REML) estimator. Between-study heterogeneity was assessed using Cochran’s Q and I² statistics. Potential publication bias was evaluated using fail-safe N methods.

Results

Two studies (n = 43,992 participants) were included. In Zhou et al. (2020), 793 strokes occurred among 19,742 nappers versus 325 strokes among 12,008 non-nappers. In Wu et al. (2024), 1,177 strokes occurred among 8,702 nappers versus 317 strokes among 2,550 non-nappers. The fixed-effect model indicated a significant association between napping and stroke (OR = 1.29; 95% CI: 1.18–1.42; p < 0.001). However, the random-effects model showed a non-significant association (OR = 1.29; 95% CI: 0.95 to 1.75; p = 0.10), with high heterogeneity (I² = 90%). Fail-safe N analyses suggested limited robustness (Rosenthal’s N = 0; Orwin’s N = 2), indicating susceptibility to publication bias.

Conclusions

Current evidence from two large cohorts suggests no significant association between daytime napping and stroke risk under a random-effects model, despite fixed-effect findings suggesting a possible association. The discrepancy likely reflects limited study number and methodological differences. Larger, well-designed prospective studies are needed to clarify causality and inform clinical guidance.

Citation

Byroju VV, Rissardo JP, Caprara AL. Daytime Napping and Ischemic Stroke Risk: Evidence from a Meta-analysis (P2-5.014). Neurology 2026;106(11_suppl_1):788. doi: 10.1212/WNL.0000000000213115.

Figure 1. Fixed-effect forest plot showing increased ischemic stroke risk among habitual nappers, driven by large cohorts.

Figure 2. Random-effects forest plot demonstrating non-significant association between daytime napping and stroke risk, with substantial heterogeneity.

Abstract - Vitamin D Supplementation in Acute Ischemic Stroke Rehabilitation: A Potential Game-changer? (P9-5.008)

Title: Vitamin D Supplementation in Acute Ischemic Stroke Rehabilitation: A Potential Game-changer? (P9-5.008)

Authors: Arthur Gribachov, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, and Vishnu Vardhan Byroju

Conference: 2026 AAN, Chicago, IL

Objective

To assess the effect of Vitamin D (VitD) supplementation versus placebo on neurological and functional recovery in patients with acute ischemic stroke (AIS) undergoing physical therapy (PT).

Background

Vitamin D deficiency is prevalent in AIS and may impair neuroplasticity and rehabilitation outcomes. Supplementation could enhance recovery, but evidence remains inconclusive.

Design/Methods

We systematically searched PubMed for randomized controlled trials comparing VitD supplementation with placebo in AIS patients receiving PT. Outcomes included NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI), modified Barthel Index (mBI), Berg Balance Scale (BBS), and Functional Ambulation Scale (FAS). Mean differences (MD) with 95% confidence intervals (CI) were pooled using fixed- and random-effects models (DerSimonian-Laird).

Results

Five trials (PMIDs: 29950783, 31181657, 32567290, 38011419, 38024000) were included. VitD significantly improved NIHSS at 3 months in the fixed-effect model (MD -1.21; 95% CI -1.801to -0.61; p < 0.01), but not in the random-effects model (MD -0.84; 95% CI -2.53 to 0.84; p = 0.32). Effects on mRS (MD -0.30; 95% CI -0.89 to 0.29) and BI (MD 0.63; 95% CI -3.03 to 4.28) were modest and inconsistent. Functional outcomes favored VitD: mBI (MD 8.85; 95% CI 7.93–9.77), FAS (MD 0.68; 95% CI 0.60–0.76), and BBS (MD 11.01; 95% CI 10.27–11.75). Heterogeneity was high (I² = 64%) due to variable dosing and follow-up.

Conclusions

VitD supplementation during the acute stroke phase, combined with PT, may enhance neurological recovery and improve balance and ambulation. However, evidence is limited by small sample sizes and methodological variability. Larger, standardized trials are needed.

Citation

Gribachov A, Rissardo JP, Caprara AL, Byroju VV. Vitamin D Supplementation in Acute Ischemic Stroke Rehabilitation: A Potential Game-changer?(P9-5.008). Neurology 2026;106(11_suppl_1):944. doi: 10.1212/WNL.0000000000213210.

Figure 1. Forest plot of NIHSS change demonstrating improved neurological outcomes with vitamin D at 3 months in fixed-effect analysis, with heterogeneity limiting consistency across studies.

Figure 2. Forest plot of mean difference in Barthel Index at 3 months comparing vitamin D versus placebo during post-stroke rehabilitation; pooled analysis shows no significant functional independence improvement.

Abstract - Bridging Therapy Triumphs? Meta-analysis Shows IVT+EVT Outperforms EVT Alone in Tandem Occlusions (P6-4.007)

Title: Bridging Therapy Triumphs? Meta-analysis Shows IVT+EVT Outperforms EVT Alone in Tandem Occlusions (P6-4.007)

Authors: Vishnu Vardhan Byroju, Jamir Pitton Rissardo, Arthur Gribachov, and Ana Leticia Fornari Caprara

Conference: 2026 AAN, Chicago, IL

 

Objective

To evaluate whether intravenous thrombolysis (IVT) combined with endovascular therapy (EVT) improves outcomes compared to EVT alone in patients with tandem occlusions.

Background

Tandem lesions, involving simultaneous extracranial and intracranial occlusions, present therapeutic challenges in acute ischemic stroke. The benefit of bridging therapy (IVT+EVT) over EVT alone remains debated.

Design/Methods

A systematic review and meta-analysis of PubMed-indexed studies was performed. Binary outcomes were pooled using the Mantel–Haenszel method under random-effects model (DerSimonian–Laird). Effect sizes were expressed as odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity was assessed with I² and Cochran’s Q. Publication bias was evaluated using Egger’s and Begg’s tests, and trim-and-fill analysis.

Results

Twenty-one studies were included. For functional independence (90-day mRS 0–2), IVT+EVT significantly improved outcomes compared to EVT alone (fixed-effect OR 1.35; 95% CI 1.16–1.57; I²=7.1%; random-effects OR 1.34; 95% CI 1.13–1.59). For successful reperfusion (mTICI 2b–3), IVT+EVT also showed benefit (fixed-effect OR 1.50; 95% CI 1.19–1.89; I²=6.9%; random-effects OR 1.48; 95% CI 1.15–1.91). For symptomatic intracranial hemorrhage, no significant difference was observed between IVT+EVT and EVT alone (fixed-effect OR 0.98; 95% CI 0.72–1.33; random-effects OR 0.97; 95% CI 0.71–1.33; I²=0%). Prediction intervals confirmed robustness, and heterogeneity was low across all analyses. Publication bias was minimal, though trim-and-fill suggested up to 3 potentially missing studies for some outcomes.

Conclusions

Bridging therapy with IVT+EVT improves functional independence and reperfusion success without increasing hemorrhagic risk in tandem occlusions. These findings support IVT administration prior to EVT when not contraindicated.

Citation

Byroju VV, Rissardo JP, Gribachov A, Caprara AL. Bridging Therapy Triumphs? Meta-analysis Shows IVT+ EVT Outperforms EVT Alone in Tandem Occlusions (P6-4.007). Neurology 2026;106(11_suppl_1):948. doi: 10.1212/WNL.0000000000213214.

Figure 1. Forest plot shows IVT+EVT improves functional independence versus EVT alone, with consistent effects and low heterogeneity.

Figure 2. Forest plot shows IVT+EVT increases successful reperfusion rates compared to EVT alone, with low heterogeneity and consistent effects.

Figure 3. Forest plot shows no significant difference in symptomatic intracranial hemorrhage between IVT+EVT and EVT alone, with no heterogeneity.

Abstract - Cannabidiol in Refractory Epilepsy: Meta-analysis of Seizure Freedom and Responder Rates Across Syndromes (P8-11.001)

Title: Cannabidiol in Refractory Epilepsy: Meta-analysis of Seizure Freedom and Responder Rates Across Syndromes (P8-11.001)

Authors: Omar Elmandouh, Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Salman Assad, Evren Burakgazi-Dalkilic, and Eric P. Nagele

Conference: 2026 AAN, Chicago, IL

 

Objective

To evaluate the efficacy of cannabidiol (CBD) in achieving seizure freedom (SF) and ≥50% responder rates (RR50) in patients with Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS), and Tuberous Sclerosis Complex (TS).

Background

CBD has emerged as an adjunctive therapy for refractory epileptic syndromes. While individual trials report benefit, pooled evidence across syndromes and doses remains essential for clinical decision-making.

Design/Methods

Randomized controlled trials (RCTs) comparing CBD to placebo in DS, LGS, and TS were identified. Outcomes included SF and RR50. Event counts and sample sizes were extracted. Odds ratios (OR) were pooled using a random-effects model (DerSimonian-Laird).

Results

A total of six RCTs comprising 604 participants in the experimental group and 599 in the control group were included. The pooled fixed-effect OR for SF was 7.93 (95% CI: 4.17–15.09), with no observed heterogeneity (I²= 0%) and a prediction interval of 3.66–16.73. Subgroup analyses revealed the greatest effect in DS at 20 mg (OR 13.35; 95% CI: 5.33–33.40) and LGS at 20 mg (OR 5.92; 95% CI: 1.03–34.17). Fail-safe N calculations (Rosenthal = 98; Orwin = 11) supported the robustness of these findings. For the outcome of 50RR, the pooled OR was 2.58 (95% CI:2.00–3.33) with a prediction interval of 1.90–3.44, again with no heterogeneity (I² = 0%). The most pronounced benefits were observed in LGS at 20 mg (OR 3.05; 95% CI: 1.84–5.04) and DS at 20 mg (OR 2.46; 95% CI: 1.46–4.14).

Conclusions

CBD significantly improves SF and 50RR in DS, LGS, and TS, with the strongest effects at 20mg. Benefits are consistent and robust, though absolute SF remains modest. Higher doses enhance efficacy but require safety considerations, supporting CBD as an effective adjunct for refractory epileptic syndromes.

Citation

D Elmandouh O, Caprara AL, Rissardo JP, Assad S, Burakgazi-Dalkilic E, Nagele EP. Cannabidiol in Refractory Epilepsy: Meta-analysis of Seizure Freedom and Responder Rates Across Syndromes (P8-11.001). Neurology 2026;106(11_suppl_1):686. doi: 10.1212/WNL.0000000000213060.

Figure 1. Forest plot shows cannabidiol significantly increases seizure freedom versus placebo across syndromes, with strongest effects at 20 mg and minimal heterogeneity.

Figure 2. Forest plot shows cannabidiol improves responder rates versus placebo across syndromes, with consistent benefits and minimal heterogeneity, greatest at 20 mg dosing.