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.

Abstract - High-resolution Ultrasound Detects Vagus Nerve Atrophy in Parkinson’s Disease: A Meta-analysis (P1-16.015)

 Title: High-resolution Ultrasound Detects Vagus Nerve Atrophy in Parkinson’s Disease: A Meta-analysis (P1-16.015)

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

Conference: 2026 AAN, Chicago, IL

 

Objective

To evaluate whether the vagus nerve (VN) cross-sectional area (CSA), measured by high-resolution ultrasound, differs between Parkinson’s disease (PD) patients and healthy controls.

Background

The VN is central to the gut-brain axis and autonomic regulation, both implicated in PD pathophysiology. High-resolution ultrasound offers a precise, non-invasive method to assess VN CSA, but case-control studies report inconsistent findings.

Design/Methods

We systematically reviewed and meta-analyzed PubMed-indexed case-control studies comparing VN CSA in PD versus controls. Standardized mean differences (SMD) were pooled using a random-effects model (DerSimonian-Laird). Subgroup analyses were performed by side (right/left) and anatomical level (thyroid and carotid-bulb). Publication bias was assessed using Egger’s and Begg’s tests and adjusted via trim-and-fill.

Results

Ten studies including 809 participants (411 PD and 398 controls) were analyzed. The pooled random-effects estimate showed significantly smaller VN CSA in PD compared to controls (SMD = -0.92; 95% CI: -1.29 to -0.55; p < 0.001). The prediction interval ranged from -2.63 to 0.79, indicating variability across studies. Subgroup analysis revealed the largest reduction at the right thyroid level (SMD = -1.69; 95% CI: -2.54 to -0.84), followed by the left thyroid level (SMD = -1.17; 95% CI: -1.69 to -0.65). At the carotid-bulb, reductions were smaller and less consistent, with pooled estimates ranging from -0.42 to -0.75. Heterogeneity was significant (Q = 221.8, p < 0.001; τ² = 0.65). Egger’s test indicated publication bias (p = 0.017), and trim-and-fill adjustment reduced the effect size to -0.66 (30.6% change). Fail-safe N using Rosenthal’s method was 442, suggesting robustness of the findings.

Conclusions

High-resolution ultrasound demonstrates significant VN CSA reduction in PD, more pronounced on the right side and at the thyroid level. Despite evidence of publication bias, findings remain robust, supporting ultrasound as a promising biomarker for autonomic involvement in PD.

Citation

De Sousa MS, Rissardo JP, Elmandouh O, Caprara AL, Walker IM. High-resolution Ultrasound Detects Vagus Nerve Atrophy in Parkinson’s Disease: A Meta-analysis (P1-16.015). Neurology 2026;106(11_suppl_1):871. doi: 10.1212/WNL.0000000000213164.

Figure 1. Forest plot shows significant vagus nerve atrophy in Parkinson’s disease versus controls, greatest at the thyroid level and right side, with substantial heterogeneity and wide prediction interval.

Abstract - Beyond Clinical Trials: Cenobamate’s Effectiveness in Diverse Epilepsy Populations (P3-10.007)

Title: Beyond Clinical Trials: Cenobamate’s Effectiveness in Diverse Epilepsy Populations (P3-10.007)

Authors: Shenney Lin, Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, April Pivonka, Kaitlyn Piotrowski, Omnea Elgendy, Matthew Petruncio, and Evren Burakgazi-Dalkilic

Conference: 2026 AAN, Chicago, IL

 

Objective

To evaluate real-world effectiveness of cenobamate in reducing seizure frequency and to characterize the demographic and clinical profiles of treated patients. 

Background

Cenobamate is a recently approved anti-seizure medication for focal epilepsy, demonstrating robust efficacy in randomized controlled trials. However, clinical trial populations often exclude patients with multiple comorbidities or complex risk factors, limiting generalizability. Real-world evidence is essential to understand its effectiveness across diverse demographic groups and clinically challenging cases, including those with psychiatric comorbidities and developmental disorders. 

Design/Methods

A retrospective cohort study was conducted involving 120 patients with focal epilepsy at a tertiary care center. Demographic data, seizure risk factors, and psychiatric comorbidities were extracted. Seizure frequency was assessed before and after at least one year of cenobamate therapy. Descriptive statistics were calculated, and a Wilcoxon signed-rank test was used to evaluate changes in seizure frequency. 

Results

The cohort had a mean age of 39.4 ± 12.3 years, with 53.3% male participants and a diverse ethnic distribution (White 55%, Black 23.3%, Hispanic 11.7%, Asian 2.5%); notable risk factors included intellectual/developmental disability in 48.3%, traumatic brain injury in 19.2%, and a family history of epilepsy in 10.8%, while psychiatric comorbidities—particularly depression and anxiety—were common. Among patients with at least one year of follow-up on cenobamate (n = 57), seizure frequency decreased significantly from 2.5 ± 2.06 seizures per week before treatment to 1.7 ± 1.3 after treatment, representing a statistically significant reduction (Wilcoxon signed-rank test: W = 1.00, p = 0.0312).

Conclusions

Cenobamate significantly reduces seizures in a real-world, diverse patient population. Effective even in patients with psychiatric and developmental comorbidities. Supports broader use beyond clinical trials. Highlights need for prospective studies for long term outcomes and optimized treatment

Citation

Lin S, Caprara AL, Rissardo JP, Pivonka A, Piotrowski K, Elgendy O, Petruncio M, Burakgazi-Dalkilic E. Beyond Clinical Trials: Cenobamate’s Effectiveness in Diverse Epilepsy Populations (P3-10.007). Neurology 2026;106(11_suppl_1):2414. doi: 10.1212/WNL.0000000000215821.

Figure 1. Pie chart showing racial distribution of patients treated with cenobamate, highlighting a majority White cohort with representation across diverse ethnic groups.

Figure 2. Pie chart illustrating prevalence of psychiatric comorbidities, with depression and anxiety most common, followed by combined conditions and none/other.

Figure 3. Pie chart showing clinical risk factors, emphasizing high prevalence of intellectual/developmental disability and notable contributions from traumatic brain injury and family history.

Abstract - Gut-brain Axis in Motion: Meta-analysis of Parkinson’s and Celiac Disease (P6-16.012)

Title: Gut-brain Axis in Motion: Meta-analysis of Parkinson’s and Celiac Disease (P6-16.012)

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

Conference: 2026 AAN, Chicago, IL

 

Objective

To evaluate the bidirectional association between Parkinson’s disease (PD) and celiac disease (CD) through meta-analysis, and to explore molecular mechanisms that may link gut and brain pathology.

Background

The gut-brain axis is increasingly recognized in the pathogenesis of neurodegenerative and autoimmune diseases. PARK7, a multifunctional protein involved in oxidative stress response, immune regulation, and epithelial barrier maintenance, has been implicated in both PD and CD. Elevated PARK7 expression in the duodenal mucosa of children with untreated CD suggests its involvement in intestinal inflammation and barrier dysfunction.

Design/Methods

A systematic review identified seven cohort studies published between 2007 and 2024 examining the association between PD and CD. Binary outcome meta-analysis was performed

using the Mantel-Haenszel method with a random effects model. Risk ratios (RR) were calculated, and heterogeneity was assessed using τ², I², and Cochran’s Q. Subgroup analyses were conducted for PD→CD and CD→PD directions. Publication bias was evaluated using Egger’s test, Begg’s test, trim-and-fill analysis, and fail-safe N methods.

Results

Four studies examined PD→CD and three examined CD→PD. For PD→CD, 38 events occurred among 54,001 PD patients vs. 149 among 138,494 controls. For CD→PD, 254 events occurred among 58,159 CD patients vs. 1,134 among 327,171 controls. The pooled risk ratio was 1.12 (95% CI: 0.98 to 1.27), p = 0.65, with low heterogeneity (I² = 0%). Subgroup estimates were: PD→CD = 0.98 (95% CI: 0.66 to 1.45), CD→PD = 1.13 (95% CI: 0.99 to 1.30). One potentially missing study was identified, with minimal impact on effect size.

Conclusions

The current study does not support bidirectional association between PD and CD. The increased expression of PARK7 in CD and its known role in PD pathophysiology highlight it as a potential molecular link in the gut-brain axis.

Citation

Adhikari Y, Rissardo JP, Shah S, Elmandouh O, Caprara AL, Walker IM. Gut-brain Axis in Motion: Meta-analysis of Parkinson’s and Celiac Disease (P6-16.012). Neurology 2026;106(11_suppl_1):624. doi: 10.1212/WNL.0000000000213025.

Figure 1. Forest plot shows no significant bidirectional association between Parkinson’s disease and celiac disease, with consistent subgroup results and low heterogeneity.

Abstract - Exploring the Association Between Parkinson’s Disease and Multiple Sclerosis: A Meta-analytic Overview (P9-17.012)

 Title: Exploring the Association Between Parkinson’s Disease and Multiple Sclerosis: A Meta-analytic Overview (P9-17.012)

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

Conference: 2026 AAN, Chicago, IL

 

Objective

To evaluate the bidirectional relationship between Parkinson’s disease (PD) and multiple sclerosis (MS), including neuromyelitis optica spectrum disorder (NMOSD), using population-based studies and meta-analytic methods.

Background

PD and MS are traditionally considered distinct neurological disorders, but emerging evidence suggests potential overlapping mechanisms. Clarifying their temporal associations may provide insight into shared pathophysiology and inform clinical practice.

Design/Methods

A systematic review of the PubMed database was conducted to identify population-based studies examining the temporal association between PD and MS, including NMOSD. Studies were included if they reported incidence data for MS following PD (PD→MS), PD following MS (MS→PD), or PD following NMOSD. Nine eligible studies were identif

ied. A meta-analysis was performed on five studies with complete comparator data using a random-effects model (DerSimonian-Laird estimator), with risk ratio (RR) as the summary measure. Subgroup analyses were conducted for each direction of association. Publication bias was assessed using Egger’s test, Begg’s test, trim-and-fill method, and fail-safe N calculations (Rosenthal, Orwin, and Rosenberg approaches).

Results

Three studies evaluated PD→MS, five assessed MS→PD, and one examined NMOSD→PD. The overall random-effects RR was 4.88 (95% CI: 1.19–20.00). Subgroup analysis showed a RR of 5.75 (95% CI: 0.44 to 75.02) for PD→MS, 7.50 (95% CI: 3.82 to 14.71) for MS→PD, and 2.22 (95% CI: 0.97 to 5.10) for NMOSD→PD. Heterogeneity was high (I² = 95%), Cochran’s Q was significant (Q = 80.5, p < 0.0001). No publication bias was detected. Rosenthal’s fail-safe N was 51, Orwin’s was 5, and Rosenberg’s was 28, indicating robustness of the findings.

Conclusions

Meta-analytic evidence suggests a potential bidirectional association between PD and MS, with a stronger link observed from MS to PD. Findings appear robust against publication bias but are limited by heterogeneity and missing comparator data.

Citation

Adhikari Y, Rissardo JP, Shah S, Elmandouh O, Caprara AL, Walker IM. Exploring the Association Between Parkinson’s Disease and Multiple Sclerosis: A Meta-analytic Overview (P9-17.012). Neurology 2026;106(11_suppl_1):623. doi: 10.1212/WNL.0000000000213024.

Figure 1. Forest plot shows a bidirectional association between Parkinson’s disease and MS, with stronger risk for MS→PD and substantial heterogeneity across studies.

Abstract - Comparative Effectiveness of Vigabatrin Versus Alternative Therapies in Infantile Spasms: A Meta-analysis of PubMed Studies (P8-11.007)

Title: Comparative Effectiveness of Vigabatrin Versus Alternative Therapies in Infantile Spasms: A Meta-analysis of PubMed Studies (P8-11.007)

Authors: 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 effectiveness of vigabatrin (VGB) compared to hormonal therapy (HRT), placebo, ketogenic diet, or combination therapy in achieving seizure freedom in infantile spasms (IS).

Background

VGB is widely used for IS, but its comparative efficacy remains debated. We synthesized evidence from randomized controlled trials (RCTs) and observational studies (OS) to clarify its role in clinical practice.

Design/Methods

We conducted a meta-analysis of 23 PubMed-indexed studies (n ≈ 2,000) reporting seizure freedom in IS patients without tuberous sclerosis complex. Random-effects models (DerSimonian-Laird) were applied using the Mantel-Haenszel method to pool risk ratios (RR) 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, trim-and-fill, and fail-safe N analyses.

Results

The random-effects model demonstrated a significant benefit of VGB (RR 0.92, 95% CI 0.84 to 0.9994). Prediction interval ranged from 0.48 to 1.50. Subgroup analyses showed consistent effects: RCTs comparing VGB vs HRT (RR 0.79; 95% CI 0.69 to 0.90) and observational studies (RR 0.76; 95% CI 0.64 to 0.90). Combination therapy (VGB + HRT) showed no clear advantage (RR 1.25; 95% CI 1.09 to 1.45). Egger’s test indicated small-study effects (p = 0.019), and trim-and-fill suggested six missing studies, reducing the effect size by 66%. Fail-safe N was 12, indicating susceptibility to publication bias.

Conclusions

VGB significantly improves seizure freedom compared to other therapies, with consistent effects across RCTs and observational studies. However, evidence of small-study effects and potential publication bias warrants cautious interpretation. Further large-scale trials are needed to confirm these findings.

Citation

Caprara AL, Rissardo JP, Assad S, Burakgazi-Dalkilic E, Nagele EP. Comparative Effectiveness of Vigabatrin Versus Alternative Therapies in Infantile Spasms: A Meta-analysis of PubMed Studies (P8-11.007). Neurology 2026;106(11_suppl):690. doi: 10.1212/WNL.0000000000213062.

Figure 1. Forest plot shows vigabatrin improves seizure freedom versus comparators, with consistent benefits across RCTs and observational studies; no added advantage with combination therapy.

Abstract - Unmasking the Risk: Aspiration Pneumonia in Parkinson’s Disease (P3-16.013)

Title: Unmasking the Risk: Aspiration Pneumonia in Parkinson’s Disease (P3-16.013)

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

Conference: 2026 AAN, Chicago, IL

 

Objective

To assess the risk of aspiration pneumonia among individuals with Parkinson’s disease (PD) compared to controls.

Background

Aspiration pneumonia is a leading cause of morbidity and mortality in PD, accounting for up to 70% of PD-related deaths. The risk is driven by oropharyngeal dysphagia, impaired cough reflex, and reduced airway protection. Despite its clinical impact, the magnitude of risk across observational studies remains uncertain, warranting meta-analytic synthesis.

Design/Methods

PubMed and Google Scholar were searched for studies comparing aspiration pneumonia risk in PD versus non-PD populations. Five observational studies (two cohort, three case-control) met inclusion criteria. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model (DerSimonian-Laird). Heterogeneity was assessed with Cochran’s Q, I², and τ². Publication bias was evaluated using trim-and-fill and fail-safe N methods.

Results

The random-effects pooled RR was 4.80 (95% CI: 2.49–9.27; p < 0.001), indicating a higher risk of aspiration pneumonia in PD, though the prediction interval was wide (0.36 to 63.55). Fixed-effect analysis yielded RR = 3.83 (95% CI: 3.81–3.85). Heterogeneity was significant (Q = 377.84, p < 0.001; τ² = 0.987), and I² was high (99%). Subgroup analysis showed a stronger association in cohort studies (RR = 8.45) than in case-control studies (RR = 4.80). No evidence of publication bias was detected (trim-and-fill: 0 missing studies). Fail-safe N was high (Rosenthal = 763; Rosenberg = 1152), suggesting robust findings.

Conclusions

PD is associated with a significantly increased risk of aspiration pneumonia, particularly in cohort studies, highlighting a critical and preventable complication. These findings emphasize the importance of early dysphagia screening, proactive airway protection strategies, and multidisciplinary interventions to reduce aspiration-related morbidity and mortality in PD. Future large-scale prospective studies are needed to refine risk estimates and guide evidence-based preventive care.

Citation

De Sousa MS, Rissardo JP, Elmandouh O, Caprara AL, Walker IM. Unmasking the Risk: Aspiration Pneumonia in Parkinson’s Disease (P3-16.013). Neurology 2026;106(11_suppl):870. doi: 10.1212/WNL.0000000000213163.

Figure 1. Forest plot shows Parkinson’s disease significantly increases aspiration pneumonia risk versus controls, with substantial heterogeneity and wide prediction interval.

Figure 2. Forest plot confirms increased aspiration pneumonia risk in Parkinson’s disease with narrower confidence intervals, despite persistent high heterogeneity across studies.

Abstract - ND0612 Infusion Dramatically Reduces OFF-time and Improves Quality of Life in Parkinson’s Disease: A Meta-analysis of Randomized Trials (P8-17.009)

Title: ND0612 Infusion Dramatically Reduces OFF-time and Improves Quality of Life in Parkinson’s Disease: A Meta-analysis of Randomized Trials (P8-17.009)

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

Conference: 2026 AAN, Chicago, IL

 

Objective

To evaluate the efficacy of ND0612 compared with placebo or current oral therapy in patients with Parkinson’s disease (PD). 

Background

Long-term oral levodopa, while an effective therapy for PD, often causes motor fluctuations with increasing OFF time and dyskinesias due to pulsatile drug levels. ND0612, a continuous subcutaneous levodopa/carbidopa infusion, aims to provide stable plasma levels and reduce OFF time. 

Design/Methods

A systematic review of PubMed and meta-analysis of randomized controlled trials comparing ND0612 with placebo or current oral regimens was conducted. Outcomes included OFF-time (hours/day), ON-time without troublesome dyskinesia, PDQ-39, PDSS, and UPDRS-III. Standardized mean differences (SMD) or mean differences (MD) with 95% confidence intervals (CI) were pooled using inverse variance methods under fixed and random-effects models. 

Results

Three trials (n = 327). OFF time: ND0612 significantly reduced OFF time compared with comparators (SMD = –0.55; p < 0.0001). ON time without dyskinesia: Increased with ND0612 (SMD = 0.54; p = 0.0047). Quality of life (PDQ-39): Improved by –2.89 points (p = 0.0049). Sleep quality (PDSS): Some benefit seen under fixed-effect model (MD = –2.11; p = 0.021), but not consistent with random-effects. Motor function (UPDRS-III): No significant change (MD = 1.41; p = 0.687). Subgroup analysis: No significant differences between placebo and current therapy comparators..

Conclusions

ND0612 significantly reduces OFF time and increases ON time without dyskinesia, improving quality of life in Parkinson’s disease patients with motor fluctuations. Effects were consistent across comparator types. Improvements in sleep and motor scores were less certain and require further study. ND0612 is a promising non-surgical option for continuous dopaminergic delivery.

Citation

Lin S, Rissardo JP, Elmandouh O, Caprara AL, Walker IM. ND0612 Infusion Dramatically Reduces OFF-time and Improves Quality of Life in Parkinson’s Disease: A Meta-analysis of Randomized Trials (P8-17.009). Neurology 2026;106(11_suppl):1166. doi: 10.1212/WNL.0000000000215020.

Figure 1. Forest plot shows ND0612 significantly reduces OFF-time versus placebo or current therapy, with consistent effects across comparator subgroups and no heterogeneity.

Figure 2. Forest plot shows ND0612 significantly improves quality of life compared to controls, with consistent findings and minimal heterogeneity.

Figure 3. Forest plot shows no significant improvement in motor scores with ND0612, with moderate heterogeneity across studies.

Abstract - Pimavanserin for Parkinson’s Disease Psychosis: A Meta-analysis of Placebo-controlled Randomized Trials (P3-17.013)

Title: Pimavanserin for Parkinson’s Disease Psychosis: A Meta-analysis of Placebo-controlled Randomized Trials (P3-17.013)

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

Conference: 2026 AAN, Chicago, IL

 

Objective

To evaluate the efficacy and safety of pimavanserin in Parkinson’s disease psychosis (PDP) through a meta-analysis of placebo-controlled randomized controlled trials (RCTs).

Background

Psychosis affects up to 60% of Parkinson’s disease patients and is associated with increased caregiver burden. Pimavanserin is the only FDA-approved drug for PDP, but its risk-benefit profile remains debated.

Design/Methods

RCTs comparing pimavanserin with placebo were identified via systematic search. The primary outcome was psychosis severity by SAPS-PD or SAPS-H+D. Secondary outcomes included UPDRS II/III and adverse events such as falls, orthostatic hypotension, and confusional state. Random-effects models were used to calculate standardized mean differences (SMD)

Results

Four trials (PMID 19907417, NCT01174004, NCT00477672, NCT00658567) were included. Pimavanserin significantly reduced psychosis severity (SMD −0.70; 95% CI −0.86 to −0.55; p < 0.01). Motor function showed no significant change (UPDRS II/III: MD −0.08; 95% CI −1.55 to 1.39; p = 0.92). Most adverse events were not significantly different from placebo, including falls (RR 0.69; 95% CI 0.42–1.12), hallucinations (RR 0.96; 95% CI 0.24–3.81), headache (RR 0.58; 95% CI 0.28–1.21), and confusional state (RR 1.42; 95% CI 0.67–3.02). Risk of orthostatic hypotension was lower with pimavanserin (RR 0.36; 95% CI 0.17–0.76). Heterogeneity was high for efficacy outcomes (I² > 90%) but low for safety outcomes.

Conclusions

Pimavanserin significantly improves psychosis in PDP without worsening motor symptoms. Most adverse events, including confusion, were not significantly different from placebo, except for a possible reduction in orthostatic hypotension. High heterogeneity and wide prediction intervals warrant cautious interpretation and further head-to-head trials.

Citation

Petruncio MG, Rissardo JP, Elmandouh O, Caprara AL, Walker IM. Pimavanserin for Parkinson’s Disease Psychosis: A Meta-analysis of Placebo-controlled Randomized Trials (P3-17.013). Neurology 2026;106(11_suppl):1176. doi: 10.1212/WNL.0000000000215026.

Figure 1. Forest plot shows pimavanserin reduces psychosis severity versus placebo in PDP, with substantial heterogeneity across trials.