Abstract - Comparing Efficacy and Safety of Various Monoclonal Antibodies in Myasthenia Gravis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials (P9-9.008)

Title: Comparing Efficacy and Safety of Different Anticoagulants in Cerebral Venous Thrombosis: A Systematic Review and Network Meta-analysis (P7-4.017)

Authors: Hassan Waseem, Zain ul Abideen, Minahil Iqbal, Saniya Ishtiaq, Justin Chen, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, Vishnu Byroju, Brandon Lucke-Wold, and Adam Dmytriw

Conference: 2026 AAN, Chicago, IL

 

Objective

This network meta-analysis aims to compare the safety and effectiveness of various doses of monoclonal antibodies used in Myasthenia Gravis (MG) treatment.

Background

MG is an autoimmune disorder that causes muscle weakness due to disrupted synaptic transmission. Several monoclonal antibodies have been developed to treat MG.

Design/Methods

PubMed, Cochrane Central, and ScienceDirect were searched through June 2025. A frequentist network meta-analysis was conducted using the “meta” and “netmeta” packages in RStudio version 4.3.3. Treatment rankings were determined by p-scores. Risk ratios (RRs) and mean differences (MD) were pooled for dichotomous and continuous outcomes to estimate the network effects. Quality assessment was done using the Cochrane Risk of Bias (RoB) 2.0 tool.

Results

Eighteen randomized controlled trials (RCTs) were included in this network meta-analysis. Rozanolixzumab (ROZ) 10 mg/kg significantly decreased the MG Activities of Daily Living (MG-ADL) score compared to placebo (MD= −2.33; 95%CI:[−3.60, −1.06]; p = 0.0003) and was ranked best (p-score = 0.77) regarding this outcome. Batoclimab (BAT) 680 mg significantly reduced the Quantitative MG (QMG) score compared to placebo (MD= −5.17; 95%CI:[−6.44, −3.89]; p <0.0001) and was rated the top performer (p-score = 0.96) for this endpoint. Regarding the MG Composite (MGC) score, BAT 340 mg was ranked best (p-score = 0.82). Eculizumab (ECU) was ranked best (p-score = 0.93) regarding the 15-item revised MG Quality of Life (MG-QoL 15r) score. Belimumab (BEL) 10 mg/kg was ranked best in terms of adverse events (p-score = 0.87).

Conclusions

ROZ 10 mg/kg ranked best for MG-ADL. BAT 680 mg significantly reduced QMG and ranked best. BAT 340 mg was best for MGC. ECU significantly decreased MG-QoL 15r and ranked best. BEL 10 mg/kg was ranked best regarding adverse events.

Citation

Waseem H, ul Abideen Z, Iqbal M, Ishtiaq S, Chen J, Rissardo JP, Caprara AL, Byroju V, Lucke-Wold B, Dmytriw A. Comparing Efficacy and Safety of Various Monoclonal Antibodies in Myasthenia Gravis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials (P9-9.008). Neurology 2026;106(11_suppl_1):567. doi: 10.1212/WNL.0000000000212994.

Figure 1. Network meta-analysis forest plots versus placebo for MG outcomes: (A) MG-ADL, (B) QMG, (C) MGC, (D) MG-QoL15r, highlighting superior efficacy rankings for ROZ, BAT, and ECU across domains.

Abstract - Comparing Efficacy and Safety of Different Anticoagulants in Cerebral Venous Thrombosis: A Systematic Review and Network Meta-analysis (P7-4.017)

Title: Comparing Efficacy and Safety of Different Anticoagulants in Cerebral Venous Thrombosis: A Systematic Review and Network Meta-analysis (P7-4.017)

Authors: Hassan Waseem, Zain ul Abideen, Jamir Pitton Rissardo, Muhammad Khan, Kanza Farhan, Justin Chen, Ana Leticia Fornari Caprara, Vishnu Byroju, Brandon Lucke-Wold, and Adam Dmytriw

Conference: 2026 AAN, Chicago, IL

 

Objective

This study aims to compare different direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs) for managing cerebral venous thrombosis (CVT) and rank them accordingly.

Background

CVT is a rare but serious type of stroke, usually treated with VKAs. However, DOACs are emerging as a new approach to anticoagulation.

Design/Methods

PubMed, Cochrane Central, and ScienceDirect were searched through May 2025. We conducted a network meta-analysis in RStudio version 4.3.3 using the “meta” and “netmeta” packages, applying a frequentist approach. P-scores ranked treatments, and risk ratios (RRs) were pooled for dichotomous outcomes to estimate network effects. The split node analysis assessed inconsistencies in direct and indirect evidence.

Results

Our analysis included 16 studies, consisting of six randomized controlled trials and ten observational studies. We found that various DOACs, including apixaban, dabigatran, and rivaroxaban, had comparable rates of complete recanalization, CVT recurrence, major hemorrhage, intracranial hemorrhage (ICH), and mortality compared to VKAs. VKAs showed the best probability of increasing complete recanalization (P-score = 0.70), while apixaban showed the worst (P-score = 0.04). Apixaban had the best probability of reducing recurrent CVT (P-score = 0.83), while dabigatran had the worst (P-score = 0.04). Apixaban also had the highest probability of reducing the risk of ICH (P-score = 0.70), while rivaroxaban had the lowest (P-score = 0.29). Apixaban has the best probability of reducing the risk of major hemorrhage (P-score = 0.81), while VKAs have the worst (P-score = 0.26). Lastly, apixaban was ranked best in reducing mortality (P-score = 0.78), while VKAs were ranked worst (P-score = 0.39).

Conclusions

DOACs showed no significant change in rates of recanalization, CVT recurrence, hemorrhage, ICH, and mortality compared to VKAs. Apixaban has the best probability of reducing the risk of CVT recurrence, mortality, and hemorrhagic events, while VKAs have the highest probability of increasing complete recanalization.

Citation

Waseem H, ul Abideen Z, Rissardo JP, Khan M, Farhan K, Chen J, Caprara AL, Byroju V, Lucke-Wold B, Dmytriw A. Comparing Efficacy and Safety of Different Anticoagulants in Cerebral Venous Thrombosis: A Systematic Review and Network Meta-analysis (P7-4.017). Neurology 2026;106(11_suppl):566. doi: 10.1212/WNL.0000000000212993.

Figure 1. Network meta-analysis forest plots comparing DOACs versus VKAs for CVT outcomes: (A) recanalization, (B) recurrence, (C) mortality, (D) major hemorrhage, showing no significant differences across treatments.

Abstract - Cerebral Embolic Protection Devices in Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-analysis of Randomized Controlled Trials (P5-4.020)

Title: Cerebral Embolic Protection Devices in Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-analysis of Randomized Controlled Trials (P5-4.020)

Authors: Rowaid Ahmad, Hassan Waseem, Zain ul Abideen, Muhammad Osama, Muhammad Haseeb Khan, Rabeya Farid, Nohela Rehman, Muhammad Ansari, Muhammad Ansari, Justin Chen, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, Vishnu Byroju, Adam Dmytriw, and Brandon Lucke-Wold

Conference: 2026 AAN, Chicago, IL

 

Objective

This meta-analysis evaluated the effectiveness and safety of cerebral embolic protection devices (CEPDs) in patients undergoing transcatheter aortic valve implantation (TAVI).

Background

Transcatheter aortic valve implantation (TAVI) is now a widely accepted treatment for patients with severe aortic stenosis. It offers a less invasive alternative to surgical aortic valve replacement (SAVR) with faster recovery and better early quality of life. However, stroke is still a major complication that can happen during or after the procedure.

Design/Methods

PubMed, Cochrane Central, and ScienceDirect were searched till April 2025. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled under a random-effects model using Review Manager version 5.4.1. The Cochrane risk of bias (RoB 2.0) tool was used for quality assessment. Funnel plots were assessed for publication bias.

Results

Eight randomized controlled trials, including 11,632 patients undergoing TAVI, were analyzed. The use of CEPDs showed a non-significant reduction in all strokes (RR 0.92, 95% CI: 0.74–1.15, p = 0.48) and disabling strokes (RR 0.80, 95% CI: 0.57–1.12, p = 0.18). There was no significant difference in all-cause mortality (RR 1.09, 95% CI: 0.71–1.67, p=0.70), disabling bleeding (RR 0.96, 95% CI: 0.28–3.31; p=0.94), and major vascular complications (RR 1.25, 95% CI: 0.56–2.78, p=0.59).

Conclusions

CEPD did not lead to significant changes in the rates of all strokes, disabling strokes, all-cause mortality, disabling bleeding, or major vascular complications. Current evidence does not support a statistically significant clinical benefit of CEPD use during TAVI. Although trends indicate a possible reduction in stroke, larger trials are necessary to confirm the significance of these findings.

Citation

Ahmad R, Waseem H, ul Abideen Z, Osama M, Khan MH, Farid R, Rehman N, Ansari M, Chen J, Rissardo JP, Fornari Caprara AL, Byroju V, Dmytriw A, Lucke-wold B. Cerebral Embolic Protection Devices in Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-analysis of Randomized Controlled Trials (P5-4.020). Neurology 2026;106(11_suppl):568. doi: 10.1212/WNL.0000000000212995.

Figure 1. Forest plot of randomized trials showing no significant reduction in all strokes (a) or in disabling strokes (b) during TAVI with CEPDs.

Abstract - Meta-analysis of DTI-Based APLS Reveals Glymphatic-related Microstructural Changes in Parkinson’s Disease

Title: Meta-analysis of DTI-Based APLS Reveals Glymphatic-related Microstructural Changes in Parkinson’s Disease (P1-16.001)

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

Conference: 2026 AAN, Chicago, IL

 

Objective

To quantify differences in DTI-APLS (diffusion tensor image analysis along the perivascular space) between Parkinson’s disease (PD) patients and healthy controls (HC) and explore its relevance to glymphatic system integrity.

Background

The glymphatic system facilitates clearance of neurotoxic proteins such as α-synuclein, and its dysfunction may contribute to PD pathogenesis. DTI metrics like APLS capture microstructural complexity and may serve as indirect markers of glymphatic efficiency. However, the magnitude and regional distribution of APLS alterations in PD remain unclear.

Design/Methods

A systematic search of PubMed identified studies reporting APLS values in PD patients and HC. Data were extracted for whole brain, left-hemisphere, and right-hemisphere. Standardized Mean Difference (SMD) as summary measure, employing DerSimonian-Laird T2 and Hedges’ g bias-corrected estimate, were performed. Fixed and random-effects models with I2 were done. Egger’s regression and funnel plot inspection were used.

Results

62 comparisons from 27 studies (2021–2025) were included. PD patients exhibited significantly lower APLS than HC (g fixed-effect –0.58 [95% CI: –0.63 to –0.53] and random-effect –0.66 [95% CI: –0.77 to –0.56]). Reductions were consistent across the whole brain (g –0.59 [95% CI: –0.67 to –0.51]), left hemisphere (g –0.60 [95% CI: –0.69 to –0.51]), and right hemisphere (g –0.55 [95% CI –0.66 to –0.43]), with no significant subgroup difference (p = 0.72). Egger’s test indicated small-study effects (p < 0.001). The adjusted effect estimate after accounting for ‘trim and fill’ analysis was g –0.50, indicating a notable change in the effect size by 25%.

Conclusions

Lower APLS in PD suggests widespread microstructural disruption potentially linked to impaired glymphatic clearance of α-synuclein and other metabolites. These findings support APLS as a promising imaging biomarker for glymphatic dysfunction in PD. Standardized protocols and longitudinal studies are needed to validate its role in early detection and therapeutic monitoring.

Citation

Rissardo JP, Caprara ALF, Walker IM. Meta-analysis of DTI-Based APLS Reveals Glymphatic-related Microstructural Changes in Parkinson’s Disease (P1-16.001). Neurology 2026;106(11_suppl):619. doi: 10.1212/WNL.0000000000213020.

Figure 1. Forest plot (whole brain) showing significantly reduced APLS in PD versus controls (pooled SMD −0.59), with moderate heterogeneity and prediction interval indicating consistent microstructural impairment.

Figure 2. Forest plot by hemisphere demonstrating reduced APLS in PD for left hemisphere (SMD −0.60), with no significant subgroup differences and moderate-to-high heterogeneity.

Abstract - Paraquat Exposure and Parkinson’s Disease Risk in the United States: A Meta-analysis of Epidemiologic Studies (P3-16.005)

Title: Paraquat Exposure and Parkinson’s Disease Risk in the United States: A Meta-analysis of Epidemiologic Studies (P3-16.005)

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

Conference: 2026 AAN, Chicago, IL

 

Objective

To quantify the association between paraquat exposure and Parkinson’s disease (PD) risk in U.S.-based studies using meta-analytic methods.

Background

Paraquat, a widely used herbicide, has been implicated as a potential environmental risk factor for PD. While numerous studies have examined this association globally, regulatory and exposure patterns differ by region. Clarifying the risk in U.S. populations is critical for public health and policy decisions.

Design/Methods

We conducted a systematic review and meta-analysis of 19 U.S.-based studies assessing paraquat exposure and PD risk. Binary outcome data were synthesized using the Mantel-Haenszel method under fixed- and random-effects models. Between-study variance (τ²) was estimated using the DerSimonian-Laird method, and heterogeneity was assessed with Cochran’s Q and I². Subgroup analyses were performed for occupational, environmental, and mixed exposure categories. Publication bias was evaluated using Egger’s, Begg’s, and Thompson-Sharp tests, as well as trim-and-fill analysis.

Results

The fixed-effects model yielded an effect size of −0.01 (95% CI: −0.09 to 0.07; p = 0.76), while the random-effects model showed −0.07 (95% CI: −0.30 to 0.15; p = 0.52). The prediction interval ranged from −0.91 to 0.76, indicating substantial uncertainty in true effects across populations. Heterogeneity was statistically significant by Q test (Q = 83.9, p < 0.001). Subgroup analyses revealed no significant associations for occupational exposure (OR 0.99; 95% CI, 0.88–1.12), environmental exposure (OR 0.98; 95% CI, 0.87–1.10), or mixed exposure (OR 3.46; 95% CI, 0.38–31.55), with all confidence intervals crossing unity. No evidence of publication bias was detected by Egger’s (p = 0.696), Begg’s (p = 0.916), or trim-and-fill methods.

Conclusions

Current U.S.-based epidemiologic evidence does not demonstrate a statistically significant association between paraquat exposure and PD risk. The wide prediction interval and significant Q test suggest variability across studies.

Citation

Rissardo JP, Caprara ALF, Walker IM. Paraquat Exposure and Parkinson’s Disease Risk in the United States: A Meta-analysis of Epidemiologic Studies (P3-16.005). Neurology 2026;106(11_suppl):620. doi: 10.1212/WNL.0000000000213021.

Figure 1. Forest plot of U.S. studies on paraquat exposure and Parkinson’s disease showing pooled odds ratios near unity across occupational, environmental, and mixed exposures, with substantial heterogeneity and wide prediction interval.

Figure 2. Funnel plot with confidence contours showing study distribution around pooled effect estimates; symmetry and formal tests indicate no significant publication bias in U.S. paraquat–PD studies.

234. Accepted

233. Accepted

Abstract - Gut check: Probiotics significantly improve gastrointestinal symptoms in Parkinson’s disease

Title: Gut check: Probiotics significantly improve gastrointestinal symptoms in Parkinson’s disease

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: 7th WPC, Phoenyx, AZ

 

Objective

To evaluate the efficacy of probiotics in alleviating gastrointestinal symptoms and motor outcomes in patients with Parkinson’s disease (PD).

Background

Constipation and gut dysbiosis are prevalent non-motor symptoms in PD, contributing to reduced quality of life and possibly influencing disease progression. Probiotics have been proposed as a therapeutic strategy to restore gut microbiota balance and improve bowel function, yet evidence remains fragmented.

Design/Methods

We conducted a systematic review and meta-analysis of placebo-controlled randomized trials indexed in PubMed. Eligible studies compared probiotics to placebo in PD patients. Outcomes included complete bowel movements (CBM) per week, Bristol Stool Scale (BSS), Patient Assessment of Constipation Quality of Life (PAC-QOL), and Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Random-effects models were applied to calculate pooled mean differences (MD) with 95% confidence intervals (CI).

Results

Five trials met inclusion criteria. Probiotics significantly increased CBM/week (MD = 1.34, 95% CI [1.04, 1.64], p < 0.001) and improved stool consistency (BSS score: MD = 0.59, 95% CI [0.36, 0.81], p < 0.001). Quality of life related to constipation improved markedly (PAC-QOL: MD = –13.94, 95% CI [–17.93, –9.95], p < 0.001). No significant effect was observed on motor function (UPDRS-III: MD = –1.50, 95% CI [–4.27, 1.27], p = 0.29). Heterogeneity was low across analyses, and publication bias was minimal.

Conclusions

Probiotics are effective in improving gastrointestinal symptoms and constipation-related quality of life in PD, with no clear impact on motor outcomes. These findings support probiotics as a safe adjunctive therapy for non-motor symptoms in PD.

Citation

Rissardo JP, Caprara ALF. Gut check: Probiotics significantly improve gastrointestinal symptoms in Parkinson’s disease. J Parkinsons Dis 2026;16(1_suppl):344-345. doi: 10.1177/1877718X261451755.

Figure 1. Forest plots show probiotics effects on CBM frequency, stool consistency, quality of life, and motor symptoms, with pooled mean differences, confidence intervals, and heterogeneity estimates.

Abstract - Parkinson’s disease risk in patients using metformin versus other antidiabetic agents: A meta-analysis of observational studies

Title: Parkinson’s disease risk in patients using metformin versus other antidiabetic agents: A meta-analysis of observational studies

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: 7th WPC, Phoenyx, AZ

 

Objective

To evaluate whether metformin use is associated with altered risk of Parkinson’s disease compared to other antidiabetic treatments.

Background

Emerging evidence suggests that type 2 diabetes mellitus may influence neurodegenerative processes, including Parkinson’s disease (PD). Metformin, a widely used antidiabetic drug, has been hypothesized to exert neuroprotective effects. However, comparative risk estimates across different glucose-lowering agents remain unclear.

Design/Methods

A systematic review and meta-analysis was conducted using PubMed-indexed observational studies comparing PD incidence among patients treated with metformin versus alternative antidiabetic therapies. Six studies (2012–2025) were included, encompassing over 500,000 participants. Risk ratios (RR) were pooled using a random-effects model (DerSimonian-Laird) with Mantel-Haenszel weighting. Subgroup analyses were performed by comparator drug class. Heterogeneity was assessed using I² and Cochran’s Q. Publication bias was evaluated via Egger’s test and trim-and-fill method.

Results

The overall pooled random-effects estimate showed no significant association between metformin use and PD risk (RR = 0.30; 95% CI: 0.47 to 1.08; p = 0.44), with substantial heterogeneity (Q = 284.07, p < 0.001). Subgroup analyses revealed reduced PD risk for metformin versus insulin (RR = 0.32; 95% CI: 0.05 to 0.95) and versus no-metformin (RR = 0.11; 95% CI: 0.59 to 0.92), but increased risk compared to SGLT2 inhibitors (RR = 1.17; 95% CI: 1.02 to 1.31). Trim-and-fill analysis suggested potential publication bias, with three missing studies and an adjusted effect estimate shifting toward null.

Conclusions

Metformin may confer differential PD risk depending on comparator therapy, with possible protective effects versus insulin and no-metformin, but higher risk compared to SGLT2 inhibitors. High heterogeneity and evidence of publication bias warrant cautious interpretation. Further prospective studies are needed to clarify metformin’s neuroprotective potential.

Citation

Rissardo JP, Caprara ALF. Parkinson’s disease risk in patients using metformin versus other antidiabetic agents: A meta-analysis of observational studies. J Parkinsons Dis 2026;16(1_suppl):71-72. doi: 10.1177/1877718X261451755.

Figure 1. Forest plot with subgroup analyses, L’Abbé and Galbraith plots assessing heterogeneity, effect size distribution, and comparative risks across metformin versus alternative therapies.

Abstract - Autoimmunity meets neurodegeneration: Is systemic lupus erythematosus protective against Parkinson’s disease?

Title: Autoimmunity meets neurodegeneration: Is systemic lupus erythematosus protective against Parkinson’s disease?

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: 7th WPC, Phoenyx, AZ

 

Objective

To evaluate whether systemic lupus erythematosus (SLE) is associated with an altered risk of Parkinson’s disease (PD) using evidence from population-based studies.

Background

Autoimmune mechanisms have been implicated in neurodegenerative disorders, but the relationship between SLE and PD remains unclear. Previous studies report conflicting results, warranting a systematic synthesis of available data.

Design/Methods

A meta-analysis was conducted following PRISMA guidelines. PubMed was searched for observational studies assessing the bidirectional association between SLE and PD. Data extracted included events and sample sizes for exposed (SLE) and control groups. Odds ratios (ORs) were pooled using Mantel–Haenszel methods under fixed and random-effects models. Heterogeneity was assessed with I² and Cochran’s Q. Publication bias was evaluated using Egger’s test and trim-and-fill analysis.

Results

Five studies met inclusion criteria. For SLE→PD, the fixed-effect model showed a significant association (OR = 0.78; 95% CI: 0.64–0.94; p = 0.01), suggesting a lower risk of PD among SLE patients. The random-effects model yielded a non-significant estimate (OR = 2.24; 95% CI: 0.71–6.99; p = 0.17) with high heterogeneity (I² = 95%). For PD→SLE, the fixed-effect model did not show association (OR = 1.24; 95% CI: 0.79–1.93). Trim-and-fill analysis indicated potential publication bias, with two missing studies and a substantial change in effect size (>150%). Fail-safe N calculations suggested susceptibility to bias.

Conclusions

Current evidence does not support a robust association between SLE and PD. While fixed-effect analysis suggests a protective trend, random-effects and bias assessments highlight uncertainty. Larger, well-controlled studies are needed to clarify this relationship.

Citation

Rissardo JP, Caprara ALF. Autoimmunity meets neurodegeneration: Is systemic lupus erythematosus protective against Parkinson’s disease?. J Parkinsons Dis 2026;16(1_suppl):68-69. doi: 10.1177/1877718X261451755.

Figure 1. Forest plots show bidirectional SLE–PD associations; Baujat and Galbraith plots identify heterogeneity contributors and outliers across studies.