A Meta-analysis of Tonic Motor Activation (TOMAC) Therapy for Restless Legs Syndrome

Title: A Meta-analysis of Tonic Motor Activation (TOMAC) Therapy for Restless Legs Syndrome

Authors: Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To evaluate the efficacy and safety of Tonic Motor Activation (TOMAC) therapy for adults with restless legs syndrome (RLS).

Background

TOMAC is a novel, wearable neuromodulation therapy designed to activate peripheral motor pathways and reduce sensorimotor symptoms in RLS. Individual trials have reported symptomatic improvement, particularly in treatment‑refractory patients, yet a comprehensive quantitative synthesis has been lacking.

Design/Methods

A meta‑analysis was performed using data extracted from PubMed‑indexed TOMAC randomized controlled trials. Primary outcomes included change in International RLS Rating Scale (IRLS) scores and responder rates on the Clinical Global Impression–Improvement (CGI‑I) and Patient Global Impression–Improvement (PGI‑I). Secondary outcomes included MOS‑I/MOS‑II sleep scales and adverse events. Analyses used inverse‑variance fixed and random‑effects models.

Results

IRLS comparisons (n=345; TOMAC=166, control=179) demonstrated significant improvement with TOMAC versus control (MD −4.06, 95% CI −4.68 to −3.44; p<0.001) with no observed heterogeneity (I²=0%) [Figure 1]. Subgroup analyses showed consistent benefit in both treatment‑naive (MD −4.57) and treatment‑refractory (MD −3.83) cohorts. Sleep outcomes (MOS‑I and MOS‑II) also favored TOMAC [MD −9.50 (95% CI −13.04 to −5.95) and MD −10.26 (95% CI −13.77 to −6.74), respectively] [Figure 2] [Figure 3]. TOMAC significantly increased clinical responder rates on CGI‑I (RR 3.89, CI 2.59–5.86) and PGI‑I (RR 3.28, CI 2.25–4.80). Adverse events were more common with TOMAC (RR 1.93, CI 1.45–2.57), predominantly mild device‑related sensations like discomfort (RR 2.11, CI 1.17–3.82); while skin changes (RR 0.99, CI 0.36–2.72) occurred at similar rates in TOMAC and sham. Discontinuation rates remained low and comparable to control (RR 2.50, CI 0.80–7.83), regardless of whether events were considered device‑related (RR 3.00, CI 0.32–28.10).

Conclusions

TOMAC therapy demonstrates clinically meaningful improvements in RLS symptom severity, sleep quality, and patient‑reported outcomes, with consistent effects across naive and refractory populations. Although mild device‑related adverse events are more frequent, overall tolerability is favorable.

Citation

Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. A Meta-analysis of Tonic Motor Activation (TOMAC) Therapy for Restless Legs Syndrome. Mov Disord 2026;41(Suppl_1):S449-S450.

Figure 1. Forest plot of pooled MD of IRLS.

Figure 2. Forest plot of pooled MD of MOS-I.

Figure 3. Forest plot of pooled MD of MOS-II.

Efficacy and Safety of Ecopipam for Tourette Syndrome: A Meta‑analysis of Controlled Trials

Title: Efficacy and Safety of Ecopipam for Tourette Syndrome: A Meta‑analysis of Controlled Trials

Authors: Ashwin Achuthaprasad, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To evaluate the efficacy and safety of ecopipam for tic reduction in Tourette syndrome (TS).

Background

Ecopipam, a selective dopamine D1 receptor antagonist, has emerged as a promising non‑D2‑blocking therapy for TS. Multiple clinical trials have examined its effects on tic severity and psychiatric comorbidities, but results have not been collectively summarized.

Design/Methods

A meta‑analytic synthesis was performed using data from PubMed trials. Outcomes included Yale Global Tic Severity Scale–Total Tic Score (YGTSS‑TTS), Clinical Global Impression–Severity (CGI‑S), and measures of depression (HAM-D, CDI, CDRS) and obsessive‑compulsive symptoms (Y-BOCS, CY-BOCS). Safety outcomes included serious (SAEs) and non‑SAEs. Mean differences (MD), standardized mean differences (SMD), and risk ratios (RR) were calculated using inverse‑variance and Mantel‑Haenszel methods.

Results

Across four trials (n=392), ecopipam significantly reduced YGTSS‑TTS versus placebo (MD −8.59; 95% CI −12.19 to −4.98) [Figure 1]. CGI‑S scores also improved (MD −0.92; 95% CI −1.08 to −0.76) [Figure 2]. Depression scores showed a small but significant benefit (SMD −0.21; 95% CI −0.39 to −0.02) [Figure 3], while obsessive‑compulsive symptom changes were not significant (SMD −0.12; 95% CI −0.36 to 0.12). SAEs were rare and did not differ from placebo (RR 1.18; 95% CI 0.41–3.45). Non‑SAEs were comparable between groups (RR 1.14; 95% CI 0.89–1.46). Insomnia (RR 2.46; 95% CI 0.37–16.14), fatigue (RR 3.26; 95% CI 0.42–25.10), and headache (RR 1.43; 95% CI 0.66–3.08) also did not differ from placebo.

Conclusions

Ecopipam demonstrates consistent, clinically meaningful reductions in tic severity, with a favorable safety profile and minimal risk of dopaminergic adverse effects. Improvements in global severity and depressive symptoms further support its therapeutic potential. These findings highlight ecopipam as a promising non‑D2‑blocking treatment option for TS, warranting continued investigation in larger, long‑term trials.

Citation

Achuthaprasad A, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Efficacy and Safety of Ecopipam for Tourette Syndrome: A Meta analysis of Controlled Trials. Mov Disord 2026;41(Suppl_1):S437-S438.

Figure 1. Forest plot of pooled MD of YGTSS‑TTS.

Figure 2. Forest plot of pooled MD of CGI-C response.

Figure 3. Forest plot of pooled SMD of depressive outcomes.

Ketogenic Diet and Motor Outcomes in Parkinson’s Disease: A Meta-analysis of Randomized Trials

Title: Ketogenic Diet and Motor Outcomes in Parkinson’s Disease: A Meta-analysis of Randomized Trials

Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Jorge Patino, Andrew McGarry, Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To evaluate the effects of ketogenic diet (KD) interventions on motor outcomes and adverse events in Parkinson’s disease (PD).

Background

Metabolic therapies such as KD have been proposed to improve mitochondrial efficiency and reduce oxidative stress in PD, potentially improving motor symptoms; however, existing trials report variable results and lack consensus on clinical impact and safety.

Design/Methods

A meta-analysis of PubMed-indexed randomized controlled trials evaluating KD in PD was performed. Extracted data included MDS-UPDRS-III and MDS-UPDRS-II in the ON state, weight, metabolic biomarkers, and adverse event risks. Effect sizes were calculated as mean differences (MD) or relative risks (RR) using inverse-variance and Mantel-Haenszel methods, applying random-effects models when appropriate.

Results

Five trials involving 129 participants were analyzed. KD did not significantly improve MDS-UPDRS-III (MD 0.97, 95% CI −1.99 to 3.92) [Figure 1] or MDS-UPDRS-II (MD −1.45, 95% CI −3.12 to 0.23) [Figure 2]. No consistent effects were observed for weight (MD 0.19, 95% CI −1.34 to 1.72) [Figure 3], glucose (MD 0.54, 95% CI −0.02 to 1.10), or triglycerides (MD 0.15, 95% CI −0.24 to 0.55). A significant reduction in A1c (MD −0.33, 95% CI −0.61 to −0.05) and an increase in total cholesterol (MD 1.57, 95% CI 1.19 to 1.95) were observed. Adverse event rates were comparable between KD and control groups, with nonsignificant relative risks for constipation (RR 3.80, 95% CI 0.18–80.57), fatigue (RR 0.73, 95% CI 0.10–5.22), and dizziness (RR 0.88, 95% CI 0.14–5.60).

Conclusions

KD did not produce significant improvements in motor function. Metabolic effects were minimal, and adverse events were comparable to controls. Larger, longer-duration studies are needed to clarify the therapeutic role of KD in PD.

Citation

Caprara AL, Rissardo JP, Patino J, McGarry A, Walker I. Ketogenic Diet and Motor Outcomes in Parkinson’s Disease: A Meta-analysis of Randomized Trials. Mov Disord 2026;41(Suppl_1): S1211-S1213.

Figure 1. Forest plot of pooled MD of motor outcomes.

Figure 2. Forest plot of pooled MD of UPDRS-II.

Figure 3. Forest plot of pooled MD of weight change.

Motor and Quality‑of‑Life Outcomes After MR‑Guided Focused Ultrasound Subthalamotomy for Parkinson’s Disease: A Meta‑analysis

Title: Motor and Quality‑of‑Life Outcomes After MR‑Guided Focused Ultrasound Subthalamotomy for Parkinson’s Disease: A Meta‑analysis

Authors: Ashwin Achuthaprasad, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To evaluate the efficacy and safety of MR‑guided focused ultrasound (MRgFUS) subthalamotomy for improving motor symptoms, medication burden, and quality of life in Parkinson’s disease (PD).

Background

MRgFUS subthalamotomy has emerged as a minimally invasive alternative for unilateral or bilateral lesioning in patients with PD. Multiple cohorts have reported improvement in motor symptoms, though variability across studies and follow‑up intervals remains. A pooled synthesis of outcomes can clarify the magnitude and durability of treatment effects.

Design/Methods

A systematic review of PubMed‑indexed clinical studies reporting pre‑ and post‑treatment outcomes of MRgFUS subthalamotomy was performed. Extracted measures included MDS‑UPDRS III (OFF), MDS-UPDRS II, PDQ‑39, and levodopa equivalent daily dose (LEDD). Adverse events (AEs) and their proportions were also collected. Random‑effects and fixed‑effect meta‑analyses were conducted across time points from 1 to 12 months.

Results

Across 5 studies (80 patients), MRgFUS subthalamotomy produced a significant improvement in MDS-UPDRS-III at all time points (MD −14.12; 95% CI −18.88 to −9.36; I2 97%) [Figure 1]. MDS-UPDRS II improved (MD −3.79; 95% CI −5.03 to −2.56; I2 0%), as did PDQ‑39 (MD −6.70; 95% CI −9.48 to −3.92; I2 0%) [Figure 2]. LEDD decreased by −148.89 mg (95% CI −210.32 to −87.45; I2 0%) [Figure 3]. Meta‑regression demonstrated that time from baseline did not significantly moderate outcomes. The most common AEs were gait ataxia (p=0.4; 95% CI 0.30–0.51), dyskinesia (p=0.35; 95% CI 0.25–0.45), dysarthria (p=0.31; 95% CI 0.22–0.42), and facial asymmetry (p=0.2; 95% CI 0.12–0.30).

Conclusions

MRgFUS subthalamotomy provides consistent, clinically meaningful reductions in motor severity, disability, and medication use up to 12 months post‑procedure. While generally well tolerated, transient gait and speech disturbances remain common. Further randomized and long‑term comparative studies are needed to refine patient selection and optimize safety.

Citation

Achuthaprasad A, Rissardo JP, Patino J,  Caprara AL, McGarry A, Walker I. Motor and Quality‑of‑Life Outcomes After MR‑Guided Focused Ultrasound Subthalamotomy for Parkinson’s Disease: A Meta‑analysis. Mov Disord 2026;41(Suppl_1):S1269-S1272.

Figure 1. Forest plot of pooled MD of motor outcomes.

Figure 2. Forest plot of pooled MD of PDQ-39 outcomes.

Figure 3. Forest plot of pooled MD of LEDD.

Clinical Impact of Nicotine in Parkinson’s Disease: Evidence from Randomized Controlled Studies

Title: Clinical Impact of Nicotine in Parkinson’s Disease: Evidence from Randomized Controlled Studies

Authors: Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To evaluate the effects of nicotine versus placebo in Parkinson’s disease (PD).

Background

Nicotine may influence dopaminergic and non‑dopaminergic pathways relevant to PD. While preclinical data suggest neuroprotective benefits, clinical trial results have been inconsistent.

Design/Methods

A meta‑analysis was conducted using PubMed‑indexed randomized controlled trials (RCTs) comparing nicotine (oral, transdermal patch, dietary) with placebo in PD. Outcomes included motor severity (MDS UPDRS‑III or equivalent), MDS UPDRS‑II, PDQ‑39/PDQ‑8, LEDD (levodopa equivalent daily dose), and adverse events. Subgroup analyses considered treatment duration (<12 weeks, 12–40 weeks, >40 weeks) and dose. Continuous outcomes were pooled using SMD and MD as appropriate. Random‑effects models with REML were used.

Results

Six studies, including 389 participants (active=203 experimental, control=186), were analyzed. Nicotine did not significantly improve motor outcomes (SMD −0.16; 95% CI −0.76 to 0.43; I² = 85%) [Figure 1] or functional disability (MD −0.65; 95% CI −1.77 to 0.47; I² = 0%). Quality‑of‑life measures showed a small but significant benefit favoring nicotine (SMD −0.26; 95% CI −0.44 to −0.07; I² = 0%) [Figure 2]. LEDD changes were nonsignificant (MD −114.40 mg; 95% CI −258.82 to 30.02; I² = 73%) [Figure 3]. Serious adverse events did not differ significantly (RR 1.97; 95% CI 0.97–4.01; I² = 0%), but total adverse events were more common with nicotine (RR 1.51; 95% CI 1.21–1.88). Nicotine increased risks of nausea (RR 3.40; 95% CI 1.81–6.39) and dizziness (RR 1.80; 95% CI 1.06–3.05), while headache, dry mouth, and palpitations showed nonsignificant associations.

Conclusions

Nicotine did not improve motor symptoms, disability, or LEDD, though it provided a small quality‑of‑life benefit. Adverse events, particularly nausea and dizziness, were more frequent. Current evidence does not support nicotine as a symptomatic therapy for PD.

Citation

Rissardo JP, Patino J,  Caprara AL, McGarry A, Walker I. Clinical Impact of Nicotine in Parkinson’s Disease: Evidence from Randomized Controlled Studies. Mov Disord 2026;41(Suppl_1):S1201-S1202.

Figure 1. Forest plot of pooled SMD of motor outcomes.

Figure 2. Forest plot of pooled SMD of quality of life outcomes.

Figure 3. Forest plot of pooled MD of LEDD.

Efficacy and Adverse Events of Tetrabenazine, Deutetrabenazine, and Valbenazine in Huntington’s Disease

Title: Efficacy and Adverse Events of Tetrabenazine, Deutetrabenazine, and Valbenazine in Huntington’s Disease

Authors: Jorge Patino, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, Andrew McGarry, Ian Walker, N. Rocha, Andrew Duker, and Erin Furr Stimming

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To compare the efficacy and safety of tetrabenazine, deutetrabenazine, and valbenazine for chorea and neuropsychiatric outcomes in Huntington’s disease (HD).

Background

VMAT2 inhibitors are standard treatments for HD chorea, yet comparative data across agents remain limited. Randomized controlled trials (RCTs) of tetrabenazine, deutetrabenazine, and valbenazine provide measurable outcomes suitable for pooled evaluation.

Design/Methods

A meta‑analysis of PubMed‑indexed RCTs evaluating VMAT2 inhibitors in HD was performed. Outcomes included change in UHDRS‑Total Maximal Chorea (TMC), depression scores (HADS/HAM-D), Clinical Global Impression–Change (CGI‑C), and adverse events. Effect sizes were calculated using inverse‑variance models for continuous outcomes and Mantel‑Haenszel methods for dichotomous outcomes.

Results

Across 283 participants, VMAT2 inhibitors significantly improved UHDRS‑TMC (MD −2.97; 95% CI −3.72 to −2.21; I2 = 0%) [Figure 1]. CGI‑C response favored active treatment (RR 3.11; 95% CI 2.02–4.78) [Figure 2]. No significant worsening of depression scores was observed (SMD −0.19; 95% CI −0.43 to 0.05) [Figure 3]. Adverse‑event rates varied by agent: somnolence was more frequent with valbenazine and tetrabenazine (RR 5.11; 95% CI 1.98–13.19), while serious adverse events (RR 1.43; 95% CI 0.36–5.66), mortality (RR 0.73; 95% CI 0.09–5.81), fatigue (RR 2.16; 95% CI 1.00–4.65), akathisia (RR 2.17; 95% CI 0.61–7.64), rash (RR 3.17; 95% CI 0.88–11.34), and falls (RR 0.95; 95% CI 0.50–1.80) did not differ significantly from controls.

Conclusions

VMAT2 inhibitors provide comparable reductions in HD chorea with favorable safety and tolerability profiles. Neuropsychiatric domains showed no significant worsening. However, subtle differences in agent-specific efficacy, side effects, and dosing schedules suggest a need for head-to-head trials to better guide individualized therapy.

Citation

Patino J, Rissardo JP, Caprara AL, McGarry A, Walker I, Rocha N, Duker A, Furr Stimming E. Efficacy and Adverse Events of Tetrabenazine, Deutetrabenazine, and Valbenazine in Huntington’s Disease. Mov Disord 2026;41(Suppl_1):S434.

Figure 1. Forest plot of pooled MD of UHDRS‑Total Maximal Chorea.

Figure 2. Forest plot of pooled RR of CGI-C response.

Figure 3. Forest plot of pooled SMD of depressive outcomes.

Efficacy and Safety of Inhaled and Sublingual Apomorphine for On-Demand Treatment of OFF Episodes in Parkinson’s Disease: A Meta‑Analysis of Randomized Placebo‑Controlled Trials

Title: Efficacy and Safety of Inhaled and Sublingual Apomorphine for On-Demand Treatment of OFF Episodes in Parkinson’s Disease: A Meta‑Analysis of Randomized Placebo‑Controlled Trials

Authors: Juan D. Martinez-Lemus, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To evaluate the efficacy and safety of inhaled (INH) and sublingual (SL) film apomorphine formulations for on-demand treatment of OFF episodes in Parkinson’s disease (PD).

Background

OFF episodes contribute substantially to disability in PD. Non‑injectable apomorphine formulations offer fast dopaminergic stimulation for on-demand symptom relief. Although INH and SL apomorphine exhibit rapid pharmacokinetics, comparative data on the magnitude,  durability, and tolerability of motor response remain limited.

Design/Methods

A systematic PubMed search identified randomized, placebo‑controlled parallel or crossover trials evaluating INH or SL apomorphine for OFF episodes in PD. The primary outcome was the change from baseline in MDS UPDRS-III scores at 30 and 60 minutes post‑dose, pooled as the mean difference (MD). Safety outcomes were summarized using risk ratios (RR). Between‑study heterogeneity was assessed with I². Random‑effects models with REML were used when heterogeneity was substantial.

Results

Four trials were included (n = 406). At 30 minutes, pooled analyses showed a greater improvement in MDS UPDRS‑III score with active treatment compared with placebo (MD −11.66 points, 95% CI −17.56 to –5.76; I² = 92%) [Figure 1]. Similar effects were observed at 60 minutes,  (MD −13.03 points, 95% CI −20.75 to –5.31; I² = 87%) [Figure 2], indicating sustained short-term motor benefit despite substantial heterogeneity. Dopaminergic adverse events occurred more frequently with active therapy, including somnolence/fatigue (RR 2.19, 95% CI 1.11–4.31) and yawning (RR 3.90, 95% CI 1.06–14.40) [Figure 3]. In contrast, nausea (RR 2.41, 95% CI 0.57–10.23) and dizziness (RR 2.71, 95% CI 0.89–8.27) did not reach statistical significance.

Conclusions

INH and SL apomorphine provide statistically significant short-term motor improvement during OFF episodes in Parkinson’s disease; however, treatment effects are highly heterogeneous, with wide prediction intervals indicating variable clinical response. Adverse events reflect expected dopaminergic effects. These findings support on-demand apomorphine as an effective option for selected patients while highlighting the need for individualized treatment selection and further comparative studies to clarify durability and tolerability.

Citation

Martinez-Lemus J, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Efficacy and Safety of Inhaled and Sublingual Apomorphine for On-Demand Treatment of OFF Episodes in Parkinson’s Disease: A Meta‑Analysis of Randomized Placebo‑Controlled Trials. Mov Disord 2026;41(Suppl_1):S1224-S1225.

Figure 1. Forest plot of pooled MD of UPDRS-III at 30 minutes.

Figure 2. Forest plot of pooled MD of UPDRS-III at 60 minutes.

Figure 3. Forest plot of pooled RR yawning.

Effects of Modafinil on Motor and Non‑Motor Outcomes in Parkinson’s Disease: A Meta‑Analysis of Randomized, Placebo‑Controlled Trials

Title: Effects of Modafinil on Motor and Non‑Motor Outcomes in Parkinson’s Disease: A Meta‑Analysis of Randomized, Placebo‑Controlled Trials

Authors: Amanda Lin, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To determine the efficacy and safety of modafinil on motor and non-motor outcomes in Parkinson’s disease (PD) using evidence exclusively from randomized placebo‑controlled clinical trials (RCTs).

Background

Modafinil, a wakefulness-promoting agent with dopaminergic and non-dopaminergic mechanisms, is used to treat excessive daytime sleepiness (EDS) and fatigue in PD. However, clinical trial results have yielded inconsistent results, and its effects on motor and non‑motor outcomes remains unclear.

Design/Methods

A systematic review and meta-analysis of PubMed‑indexed RCTs evaluating modafinil in idiopathic PD were performed. Extracted outcomes included EDS (Epworth Sleepiness Scale – ESS), fatigue (Fatigue Severity Scale – FSS), motor function (MDS-UPDRS III and total scores), and depressive symptoms (Beck & Hamilton depression scales). Effect estimates were pooled using fixed and random‑effects models with REML, as appropriate. Standardized mean differences (SMD) and mean differences (MD) were applied. Adverse events were analyzed using relative risks (RR).

Results

Eight trials including 216 participants (modafinil = 113, placebo = 103) met inclusion criteria. Modafinil significantly improved EDS compared with placebo (MD −2.12 points; 95% CI −3.64 to −0.60; I² = 65%), though meta‑regression showed no association between treatment duration and response. No significant differences were observed in motor outcomes (SMD = 0.20; 95% CI −0.23 to 0.63). Modafinil did not significantly improve fatigue (MD = −0.17; 95% CI −1.12 to 0.79) or depressive symptoms (MD = 1.51; 95% CI −0.10 to 3.11) [Figure 3]. Adverse events, including insomnia (RR 0.72; 0.17–3.10), headache (RR 0.73; 0.21–2.50), dizziness (RR 1.69; 0.36–7.96), and gastrointestinal symptoms (RR 2.57; 0.53–12.48), were infrequent and did not differ significantly from placebo.

Conclusions

In RCTs involving PD patients, modafinil is associated with a modest improvement in EDS without significant effects on motor function, fatigue, or mood. The absence of motor worsening or significant adverse events supports short-term tolerability. However, heterogeneity across studies and limited sample sizes limit confidence in effect estimates. Larger, adequately powered trials are needed to clarify the clinical role of modafinil in PD.

Citation

Lin A, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Effects of Modafinil on Motor and Non‑Motor Outcomes in Parkinson’s Disease: A Meta‑Analysis of Randomized, Placebo‑Controlled Trials. Mov Disord 2026;41(Suppl_1):S1247-S1249.

Figure 1. Forest plot of pooled MD of EDS.

Figure 2. Forest plot of pooled SMD of motor outcomes.

Figure 3. Forest plot of pooled MD of depressive outcomes.

Comparative Motor Response to Bilateral STN‑DBS in LRRK2‑Related and Idiopathic Parkinson’s Disease

Title: Comparative Motor Response to Bilateral STN‑DBS in LRRK2‑Related and Idiopathic Parkinson’s Disease

Authors: Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To compare motor improvement after subthalamic nucleus deep brain stimulation (STN‑DBS) in patients with LRRK2‑associated Parkinson’s disease (PD) versus idiopathic PD (iPD).

Background

LRRK2 mutations (G2019S, R1441G, G2385R) represent the most common genetic cause of autosomal dominant PD. STN‑DBS generally improves motor symptoms in iPD, yet whether genetic status modifies treatment response remains unclear.

Design/Methods

A meta‑analysis was performed using PubMed studies reporting MDS UPDRS‑III outcomes in LRRK2‑PD versus iPD following bilateral STN‑DBS. Mean differences (MD) in MDS UPDRS‑III improvement (OFF-medication) were pooled using inverse‑variance methods under arandom‑effects model. Heterogeneity and subgroup analyses (G2019S, R1441G, G2385R) were conducted. Mixed‑effects REML meta‑regression examined whether age, DBS duration, or study quality moderated DBS outcomes.

Results

Seven studies (n=392; 73 LRRK2 carriers, 319 iPD) were included. There was no significant difference in MDS UPDRS‑III improvement between LRRK2‑PD and iPD using a random‑effects model (MD −3.26; 95% CI −8.81 to 2.29; I²=58%) [Figure 1][Figure 2]. Mutation subgroup analysis revealed no significant differences between G2019S, R1441G, or G2385R carriers (QM p=0.45). Meta‑regression identified DBS duration as the only significant moderator: duration categories explained most between‑study variability (R²=97.2%), reducing I² to 4% with no residual heterogeneity. Compared with 12 months, the 6–12 months group showed greater improvement (β=10.55±3.57, p=0.003), while the ≤6-months group showed a positive but nonsignificant trend (β=14.86±9.29, p=0.11). Age (p=0.84) and study quality (p=0.29) did not moderate outcomes.

Conclusions

Motor outcomes after STN‑DBS in LRRK2‑associated PD are comparable to those of iPD. No specific LRRK2 mutation subtype showed a differential response. DBS duration, rather than genotype, emerged as the only significant moderator of DBS motor benefit. This may reflect early optimization needs and later disability accrual, underscoring need for longer follow‑up. These findings support comparable DBS candidacy considerations for LRRK2‑PD and iPD.

Citation

Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Comparative Motor Response to Bilateral STN‑DBS in LRRK2‑Related and Idiopathic Parkinson’s Disease. Mov Disord 2026;41(Suppl_1):S1300-S1301.

Figure 1. Forest plot of pooled MD of motor outcomes.

Figure 2. Funnel plot with confidence intervals of the studies included.

Subthalamic Deep Brain Stimulation Produces Consistent Improvements in Sleep Quality and Daytime Sleepiness in Parkinson’s Disease: A Systematic Review and Meta-analysis

Title: Subthalamic Deep Brain Stimulation Produces Consistent Improvements in Sleep Quality and Daytime Sleepiness in Parkinson’s Disease: A Systematic Review and Meta-analysis

Authors: Mya C. Schiess, Juan D. Martinez-Lemus, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

This study aims to determine the effects of subthalamic nucleus deep brain stimulation (STN‑DBS) on sleep quality and daytime sleepiness in Parkinson’s disease (PD).

Background

Sleep disturbances are among the most prevalent and disabling non‑motor symptoms (NMS) in PD. While STN‑DBS is an established therapy for motor symptoms, its impact on nocturnal sleep quality and daytime somnolence remains variably reported. The Parkinson’s Disease Sleep Scale (PDSS) and the Epworth Sleepiness Scale (ESS) provide validated frameworks for assessing distinct dimensions of sleep dysfunction.

Design/Methods

A systematic review and meta-analysis of longitudinal unilateral and bilateral STN‑DBS studies were conducted using PubMed-indexed articles. Nine studies reporting PDSS outcomes (n =286) and eight studies reporting ESS outcomes (n =190) were included. Extracted variables included sample sizes, mean change from baseline, standard errors, and follow-up duration. Data were synthesized using an inverse‑variance model with fixed‑effects. Heterogeneity was assessed using I² and tau², and prediction intervals were calculated.

Results

Most participants (93.68%) underwent bilateral STN‑DBS. STN‑DBS was associated with a significant pooled mean change from baseline in PDSS scores of 21.23 points (95% CI: 11.59 to 30.87) indicating substantial improvement in overall sleep quality [Figure 1]. Improvement peaked at six months. Heterogeneity was negligible (I² = 0%; tau² = 0), with a  prediction interval of 9.61 to 32.86.  ESS outcomes also improved significantly, with a pooled mean change from baseline of –3.62 (95% CI: –5.09 to –2.14) [Figure 2]. Heterogeneity for ESS was also minimal (I² = 0%; tau² = 0).

Conclusions

STN‑DBS yields robust and reproducible improvements in both nocturnal sleep quality and daytime somnolence in PD. The consistency across PDSS and ESS outcomes supports the utility of DBS for sleep‑related NMS and highlights the value of standardized measurement tools in evaluating DBS effects.

Citation

Schiess MC, Martinez-Lemus JD, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Subthalamic Deep Brain Stimulation Produces Consistent Improvements in Sleep Quality and Daytime Sleepiness in Parkinson’s Disease: A Systematic Review and Meta-analysis. Mov Disord 2026;41(Suppl_1):S1304-S1306.

Figure 1. Forest plot of pooled mean change from baseline in MD of PDSS scores after STN-DBS.

Figure 2. Forest plot of pooled mean change from baseline in MD of ESS scores after STN-DBS.