Levetiracetam Versus Phenobarbital as First‑Line Therapy for Neonatal Seizures: A Meta‑analysis of Randomized Controlled Trials

Title: Levetiracetam Versus Phenobarbital as First‑Line Therapy for Neonatal Seizures: A Meta‑analysis of Randomized Controlled Trials

Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo

Conference: 2026 ANA Annual Meeting, San Diego, CA

OBJECTIVE

Phenobarbital remains the standard first‑line treatment (1LT) for neonatal seizures (NS) despite concerns regarding efficacy and safety. Levetiracetam has gained widespread use as an alternative, but randomized evidence is conflicting. We performed a meta‑analysis of randomized controlled trials (RCTs) comparing levetiracetam with phenobarbital as 1LT for NS.

METHODS

We systematically identified RCTs PubMed-indexed enrolling neonates treated with levetiracetam or phenobarbital as initial antiseizure medication (ASM). The primary outcome was seizure freedom (SF) within 24 hours. Secondary outcomes included 1LT failure, requirement for rescue ASM, adverse events (AEs), and mortality. Risk ratios (RRs) were pooled using a Mantel–Haenszel random‑effects model with REML. Heterogeneity was quantified using the I2 statistic. Numbers needed to treat (NNT) and harm (NNH) were estimated from absolute risk differences.

RESULTS

Six RCTs (levetiracetam=245; phenobarbital=216) were included. Levetiracetam did not significantly increase SF compared with phenobarbital (RR 1.23, 95% CI 0.86–1.76; I2=72%). On meta‑regression, trials using clinical seizure diagnosis demonstrated higher SF rates with levetiracetam (RR  1.38, 95% CI 1.01–1.88), whereas the single trial using continuous EEG‑confirmed seizures showed superior efficacy of phenobarbital (RR 0.30, 95% CI 0.17–0.54). 1LT failure (RR  0.87, 95% CI 0.52–1.44) and need for rescue ASM (RR 0.73, 95% CI 0.46–1.17) did not differ significantly between groups. Levetiracetam was associated with fewer AEs overall (RR 0.33, 95% CI 0.15–0.71), particularly hypotension (RR 0.30, 95% CI 0.13–0.68). No differences were observed between groups for respiratory depression (RR 0.63, 95% CI 0.32–1.25), bradycardia (RR 0.44, 95% CI 0.13–1.53), or mortality rates (RR 1.17, 95% CI 0.46–2.95). Levetiracetam increased SF by 3.3% (NNT ≈ 30), whereas phenobarbital increased hypotension by 9.1% (NNH ≈ 11).

CONCLUSIONS

Levetiracetam does not demonstrate consistent superiority over phenobarbital as 1LT for NS control. However, levetiracetam shows a more favorable short‑term safety profile. RCTs assessing different NS diagnoses are needed to confirm results.

Citation

Caprara AL, Rissardo JP. Levetiracetam Versus Phenobarbital as First‑Line Therapy for Neonatal Seizures: A Meta‑analysis of Randomized Controlled Trials. Ann Neurol 2026;100(Suppl 37):S160.

Deferiprone in Parkinson’s Disease: Motor, Imaging, and Safety Outcomes Across Randomized Trials

Title: Deferiprone in Parkinson’s Disease: Motor, Imaging, and Safety Outcomes Across Randomized Trials

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: 2026 ANA Annual Meeting, San Diego, CA

BACKGROUND/OBJECTIVE

Iron accumulation in the substantia nigra (SN) contributes to oxidative injury and neurodegeneration in Parkinson’s disease (PD). Deferiprone (DFP), a brain‑penetrant iron chelator, has been evaluated as a potential disease‑modifying therapy, with inconsistent trial‑level results. We conducted a systematic review and meta‑analysis of randomized controlled trials (RCTs) to quantify the effects of DFP on motor outcomes, neuroimaging biomarkers, and safety in PD.

DESIGN/METHODS

Pubmed and ClinicalTrials.gov were searched for RCTs comparing DFP versus placebo in PD. Random‑effects meta‑analyses (REML estimator) were performed. Outcomes assessed were motor (MDS‑UPDRS Part III), MRI iron measures (SN, caudate, and putamen), serum ferritin, cognition, (MoCA/MMSE), quality-of-life (PDQ‑39), and adverse events. Effect sizes were expressed as standardized mean differences (SMD) or mean differences (MD). Heterogeneity was quantified using I2.

RESULTS

Four RCTs (n = 474 participants) were included. Pooled analysis demonstrated no significant improvement in motor symptoms with DFP versus placebo (SMD −0.11, 95% CI −0.43 to 0.21; p = 0.51; I2 = 0%). Dose‑stratified 9‑month analyses showed no significant effect across 300–1200 mg/day (MD 0.30, 95% CI −1.93 to 2.52; I2 = 64%). MRI iron outcomes showed no significant pooled effect in the SN (SMD 0.20, 95% CI −0.78 to 1.19; I2 = 79%), caudate (SMD −0.05, 95% CI −1.20 to 1.11), or putamen (SMD 0.01, 95% CI −0.95 to 0.96). DFP significantly reduced serum ferritin (MD −45.4 ng/mL, 95% CI −78.0 to −12.9; p = 0.006; I2 = 0%). No significant between‑group difference were observed for quality-of-life (MD 1.04, 95% CI −3.26 to 5.33) and cognition (SMD −0.10, 95% CI −0.48 to 0.28; p = 0.62). Risk of any adverse event was higher with DFP (RR 1.49, 95% CI 1.23–1.81; p < 0.001), with a non‑significant increase in serious adverse events and hematologic toxicity.

CONCLUSIONS

Across randomized evidence, deferiprone does not improve motor, cognitive, or quality‑of‑life outcomes in PD despite demonstrable iron chelation. Increased adverse events and lack of clinical efficacy do not support routine use of DFP as symptomatic or disease‑modifying therapy in PD.

Citation

Rissardo JP, Caprara AL. Deferiprone in Parkinson’s Disease: Motor, Imaging, and Safety Outcomes Across Randomized Trials. Ann Neurol 2026;100(Suppl 37):S311.

Escitalopram for Depression and Motor Symptoms in Parkinson’s Disease: A Systematic Review and Meta‑analysis

Title: Escitalopram for Depression and Motor Symptoms in Parkinson’s Disease: A Systematic Review and Meta‑analysis

Authors: Vishnu V. Byroju, 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 of escitalopram versus placebo for depressive symptoms, motor severity, and quality of life (QoL) in Parkinson’s disease (PD).

Background

Depression is highly prevalent in PD and contributes to disability and reduced QoL. Although selective serotonin reuptake inhibitors are frequently prescribed, evidence regarding the impact of escitalopram on mood and motor outcomes in PD remains inconsistent.

Design/Methods

A PRISMA‑compliant systematic search of PubMed, Embase, Cochrane Library, Scopus, Web of Science, PsycINFO, and CNKI identified randomized controlled trials (RCTs) comparing escitalopram with placebo in adults with PD. Outcomes included depressive symptoms [Hamilton Depression Rating Scale (HAM‑D), Beck’s Depression Inventory (BDI‑II), and Patient Health Questionnaire-9 (PHQ‑9)], motor severity [Unified Parkinson’s Disease Rating Scale III (UPDRS‑III)], and quality of life [Parkinson’s Disease Questionnaire-39 (PDQ‑39)]. Standardized mean differences (SMDs) or mean differences (MDs) were synthesized using random‑effects models (REML). Heterogeneity was assessed using I².

Results

Four RCTs (escitalopram n=124; placebo n=126) met inclusion criteria. Escitalopram improved depressive symptoms compared with placebo (SMD −1.25; 95% CI −2.33 to −0.16), but with very high heterogeneity (I²=92.1%). No significant effect was observed for UPDRS‑III (MD −2.18; 95% CI −11.11 to 6.76; I²=98%). QoL modestly improved with escitalopram (PDQ‑39 MD −6.47; 95% CI −10.83 to −2.11). Rates of adverse events, including constipation (RR 3.50, 95% CI 0.18–69.24), dyspepsia (RR 0.70, 95% CI 0.01–33.90), falls (RR 3.50, 95% CI 0.18–69.24), fatigue (RR 1.38, 95% CI 0.13–14.20), dizziness (RR 0.70, 95% CI 0.01–33.90), and insomnia (RR 0.23, 95% CI 0.01–5.45), did not differ meaningfully between groups.

Conclusions

Escitalopram may reduce depressive symptoms and improve QoL in PD, although the evidence is limited by small sample sizes, substantial heterogeneity, and imprecise estimates. Motor outcomes show no consistent effect. Larger, methodologically uniform RCTs are needed to clarify escitalopram’s efficacy and safety in PD.

Citation

Byroju V, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Escitalopram for Depression and Motor Symptoms in Parkinson’s Disease: A Systematic Review and Meta‑analysis. Mov Disord 2026;41(Suppl_1):S689.

Bidirectional Association Between Gout and Parkinson’s Disease: A Systematic Review and Meta-Analysis

Title: Bidirectional Association Between Gout and Parkinson’s Disease: A Systematic Review and Meta-Analysis

Authors: Vishnu V. Byroju, 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 whether gout influences the risk of Parkinson’s disease (PD) and whether PD influences the subsequent risk of gout.

Background

Gout and PD share potential mechanistic pathways involving urate metabolism, oxidative stress, and neuroinflammation. However, epidemiologic studies examining their association have produced inconsistent findings.

Design/Methods

A PubMed search identified studies reporting hazard ratios (HRs) for gout preceding PD (Gout→PD) and PD preceding gout (PD→Gout). Random‑effects models with inverse‑variance weighting were applied. Sex‑stratified analyses were performed when available. Heterogeneity was quantified using I², and publication bias was evaluated using trim‑and‑fill and multiple fail‑safe N methods.

Results

Five studies provided thirteen study‑level estimates of gout to PD risk [Figure 1]. The pooled HR was 2.86 (95% CI 2.76–2.96; I² = 74.5%). Female‑specific analyses showed HR 3.21 (95% CI 2.91–3.55), and male‑specific analyses showed HR 2.61 (95% CI 2.45–2.79). Trim‑and‑fill identified no missing studies, and Rosenthal’s fail‑safe N was 831. Two studies evaluated PD to gout risk [Figure 2], yielding a pooled HR of 1.65 (95% CI 1.42–1.90; I² = 0%). Females had HR 1.75 (95% CI 1.36–2.26), and males HR 1.60 (95% CI 1.34–1.91). The fail‑safe N was 1, reflecting the limited available evidence.

Conclusions

Gout was associated with a higher risk of PD, and PD was associated with a higher risk of subsequent gout. These findings suggest shared pathways involving systemic inflammation, purine metabolism, and urate regulation. Further mechanistic and longitudinal studies are needed to clarify how these biological processes link gout and PD.

Citation

Byroju V, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Bidirectional Association Between Gout and Parkinson’s Disease: A Systematic Review and Meta-Analysis. Mov Disord 2026;41(Suppl_1):S757-S758.

Figure 1. Gout to PD risk.

Figure 2. PD to gout risk.

Risk of Deep Venous Thrombosis in Patients With Parkinson’s Disease: A Meta‑Analysis of Observational Studies

Title: Risk of Deep Venous Thrombosis in Patients With Parkinson’s Disease: A Meta‑Analysis of Observational Studies

Authors: Vishnu V. Byroju, 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 compare the risk of deep venous thrombosis (DVT) in patients with Parkinson’s disease (PD) versus non‑PD.

Background

Patients with PD may have an elevated DVT risk due to immobility, autonomic dysfunction, and reduced muscle pumping. However, evidence has been inconsistent across surgical and nonsurgical populations.

Design/Methods

PubMed‑indexed studies reporting DVT incidence in PD versus non‑PD patients were screened. Risk ratios (RRs) were pooled using Mantel‑Haenszel (fixed) and REML (random effects) models. Subgroup analyses included study design, geographic region, and surgery type.

Results

Across 16 studies comprising 819,514 patients, 2,176 DVT events occurred. PD patients demonstrated a significantly higher risk of DVT compared with non‑PD controls (random‑effects RR 2.23, 95% CI 1.41–3.53). Heterogeneity was moderate to high (I² = 67%). Subgroup analyses showed elevated risk in cohort studies (RR 1.37, 95% CI 1.10–1.71) and cross‑sectional studies (RR 6.82, 95% CI 4.05–11.48), while case‑control studies demonstrated a non‑significant association (RR 1.44, 95% CI 0.90–2.31)[Figure 1]. Regionally, the highest risk was observed in Asian studies (RR 6.04, 95% CI 3.26–11.19), followed by North America (RR 1.71, 95% CI 1.08–2.71). Associations from Europe (RR 2.41, 95% CI 0.30–19.15) and Australia (RR 3.49, 95% CI 0.38–32.32) were not statistically significant [Figure 2]. By surgical category, nonsurgical cohorts demonstrated the greatest risk (RR 6.07, 95% CI 3.20–11.49), followed by spine surgery (RR 2.45, 95% CI 1.19–5.04) and orthopedic procedures (RR 1.29, 95% CI 1.01–1.63). No significant increase in risk was observed for DBS surgery (RR 2.27, 95% CI 0.12–41.75) or mixed surgical groups [Figure 3].

Conclusions

PD is associated with a significantly increased risk of DVT across study types and clinical settings. The magnitude of risk varies by geography and surgical context, suggesting that underlying population and perioperative factors are at play.

Citation

Byroju V, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Risk of Deep Venous Thrombosis in Patients With Parkinson’s Disease: A Meta‑Analysis of Observational Studies. Mov Disord 2026;41(Suppl_1):S758-S761.

Figure 1. DVT risk in PD across study designs.

Figure 2. DVT risk in PD across regions.

Figure 3. DVT risk in PD across surgery type.

Antidepressants in Huntington’s Disease: A Meta Analysis of Mood and Motor Outcomes with Placebo-controlled Trials

Title: Antidepressants in Huntington’s Disease: A Meta Analysis of Mood and Motor Outcomes with Placebo-controlled Trials

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 evaluate the antidepressant efficacy for depression in Huntington’s disease (HD).

Background

Depression is highly prevalent in HD. Despite frequent clinical use of antidepressants, evidence from trials remains limited and fragmented. A consolidated analysis of available trials data is needed to guide treatment decisions.

Design/Methods

PubMed was searched for trials evaluating antidepressant drugs in HD. The primary endpoint was depression (HAM‑D). Secondary endpoints included anxiety (SAS), motor function (UHDRS‑TMS), cognition (MMSE, NPI), functional capacity (UHDRS‑TFC), executive function (Trails‑B), and adverse events. Mean differences (MDs) were synthesized using inverse‑variance models, and SMD with REML.

Results

A total of 4 trials studying fluoxetine, venlafaxine, citalopram, and bupropion were found. For bupropion, only data about side effects were available. Antidepressants significantly improved depression versus control (MD −4.52, 95% CI −8.85 to −0.20; I² = 86%) [Figure 1]. Subgroup effects varied by medication (fluoxetine MD −2.87; venlafaxine MD −9.08; citalopram MD −1.90). Anxiety improved modestly (SMD −0.62, 95% CI −1.17 to −0.08) [Figure 2]. No significant effects were observed for functional (MD –0.27, 95% CI –1.37 to 0.82) [Figure 3], executive (SMD -0.12, 95% CI –1.11 to 0.88), motor (SMD –0.37, 95% CI –0.91 to 0.17), or cognitive (SMD –0.21, 95% CI –0.75 to 0.32) outcomes. Adverse event rates were similar between antidepressant and placebo groups (RR 1.86, 95% CI 0.73–4.75). Agitation (RR 0.71, 95% CI 0.17–3.01), hypomania (RR 0.95, 95% CI 0.25–3.65), fatigue (RR 0.31, 95% CI 0.01–6.85), and weight loss (RR 2.77, 95% CI 0.12–61.65) occurred at comparable frequencies.

Conclusions

Evidence indicates antidepressants yield a modest yet significant reduction in depressive symptoms in HD, though effects differ by drug class. Benefits seem confined to mood outcomes, with no consistent improvement in motor, cognitive, or functional measures. Larger, adequately powered trials are needed to guide optimal treatment strategies.

Citation

Patino J, Rissardo JP, Caprara AL, McGarry A, Walker I, Rocha N, Duker A, Furr Stimming E. Antidepressants in Huntington’s Disease: A Meta Analysis of Mood and Motor Outcomes with Placebo-controlled Trials. Mov Disord 2026;41(Suppl_1):S433-S434.

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

Figure 2. Forest plot of pooled MD of anxiety outcomes.

Figure 3. Forest plot of pooled MD of functional capacity outcomes.

Efficacy of Vitamin C for Restless Legs Syndrome: A Systematic Review and Meta‑analysis of Randomized Controlled Trials

Title: Efficacy of Vitamin C for Restless Legs Syndrome: A Systematic Review and Meta‑analysis of Randomized Controlled 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 efficacy and safety of vitamin C (VITC) for treating restless legs syndrome (RLS) using evidence exclusively from randomized controlled trials (RCTs).

Background

VITC has been proposed as a potential therapy for RLS due to its antioxidant properties and possible modulation of dopaminergic pathways. Several RCTs have assessed its impact on symptom severity and related clinical outcomes, but findings have been inconsistent.

Design/Methods

A systematic review of PubMed and Google Scholar of RCTs comparing VITC to placebo or active comparators in adults with RLS was conducted. The primary outcome was change in International Restless Legs Scale (IRLS) scores. Secondary outcomes included itching, categorical RLS symptom severity, and sleep disturbance. Adverse events such as nausea and dyspepsia were also investigated. Random‑ and fixed‑effects models were applied. Heterogeneity was quantified using I².

Results

Four RCT arms from two studies contributed to the IRLS analysis (n=119). In subgroup analysis, VITC was significantly more effective than placebo (MD –8.12 points; 95% CI –11.52 to –4.71; p<0.001), while demonstrating no meaningful difference compared with vitamin E (MD 0.10; 95% CI –3.42 to 3.62) or pramipexole (MD 0.59; 95% CI –4.18 to 5.36) [Figure 1]. VITC also improved sleep outcomes (RD 0.36; 95% CI 0.17 to 0.54; p<0.001). However, effects on itching (RR 0.82; 95% CI 0.18–3.75) and global RLS severity (RR 0.80; 95% CI 0.20–3.31) varied substantially across subgroups, reflecting heterogeneity in clinical response. Nausea (RR 0.32; 95% CI 0.04–2.94) [Figure 2] and dyspepsia (RR 3.00; 95% CI 0.33–27.33) [Figure 3] remained infrequent adverse events and did not differ significantly between treatment groups.

Conclusions

VITC may reduce RLS severity compared with placebo, though benefits are inconsistent across comparators and limited by high heterogeneity. Evidence for secondary outcomes is mixed and largely derived from single‑study data. Larger, rigorously designed RCTs are needed to clarify VITC’s therapeutic role in RLS.

Citation

Caprara AL, Rissardo JP, Patino J, McGarry A, Walker I. Efficacy of Vitamin C for Restless Legs Syndrome: A Systematic Review and Meta‑analysis of Randomized Controlled Trials. Mov Disord 2026;41(Suppl_1):S448-S449.

Figure 1. Forest plot of pooled MD of IRLS.

Figure 2. Forest plot of pooled RR of nausea.

Figure 3. Forest plot of pooled RR of dispepsia.

Efficacy and Safety of Mesdopetam (IRL790) for Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta analysis of Randomized Controlled Trials

Title: Efficacy and Safety of Mesdopetam (IRL790) for Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta analysis of Randomized 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 mesdopetam compared with placebo for levodopa‑induced dyskinesia (LID) in Parkinson’s disease (PD).

Background

Mesdopetam (IRL790) is a selective dopamine D3‑receptor antagonist developed to reduce LID without worsening parkinsonism. Multiple randomized trials have investigated its clinical effects across different dose ranges, but results have varied.

Design/Methods

A meta‑analysis of randomized, double‑blind, placebo‑controlled trials was conducted using studies registered on ClinicalTrials.gov to ensure methodological rigor and consistency. Outcomes extracted included the UDysRS total score, ON-time without troublesome dyskinesia (hours), OFF time (hours), MDS-UPDRS‑IV, activities of daily living (MDS-UPDRS‑II), and adverse events (AEs). Mean differences (MD), standardized mean differences (SMD), and risk ratios (RR) for dichotomous outcomes were pooled using inverse‑variance statistical models.

Results

Across 3 studies (n = 323), mesdopetam was non-significant for dyskinesia severity reduction (MD –1.77 points, 95% CI –4.07 to 0.54) [Figure 1]. ON-time without troublesome dyskinesia improvement was nonsignificant (MD –0.47 h, 95% CI –1.25 to 0.31) [Figure 2]. OFF time decreased significantly (MD –0.61 h, 95% CI –1.16 to –0.07) [Figure 3]. UPDRS-IV (MD –0.15 points, 95% CI –0.37 to 0.07) and activities of daily living (SMD –0.17, 95% CI –0.39 to 0.06) were not significant. Overall, any AEs (RR 1.12, 95% CI 0.94–1.34), serious AEs (RR 0.45, 95% CI 0.14–1.42), and falls (RR 1.09, 95% CI 0.45–2.59) were comparable between groups. Fatigue occurred less frequently with mesdopetam, showing a protective effect (RR 0.23, 95% CI 0.06–0.81).

Conclusions

Mesdopetam appears safe and modestly effective for LID, with small improvements in dyskinesia severity and OFF time and no worsening of motor disability. Larger trials are warranted to clarify optimal dosing and confirm clinical benefit.

Citation

Achuthaprasad A, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Efficacy and Safety of Mesdopetam (IRL790) for Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta analysis of Randomized Controlled Trials. Mov Disord 2026;41(Suppl_1):S1204-S1205.

Figure 1. Forest plot of pooled MD of UDysRS total score.

Figure 2. Forest plot of pooled MD of ON-time without troublesome dyskinesia.

Figure 3. Forest plot of pooled MD of OFF-time.

Abstracts - 2027

2027

NANS 2027 Annual Meeting - Las Vegas, NV

Motor Outcomes After Deep Brain Stimulation in GBA vs Non‑GBA Parkinson’s Disease: A Meta‑analysis

Medication-State–Specific Effects of Deep Brain Stimulation on Freezing of Gait in Parkinson’s Disease

Deep Brain Stimulation of the Anterior Limb of the Internal Capsule for Obsessive–Compulsive Disorder

Awake Versus Asleep Deep Brain Stimulation for Parkinson’s Disease: A Meta‑Analysis of Motor Outcomes

Robotics‑Assisted Versus Conventional Techniques in Deep Brain Stimulation: A Systematic Review and Meta‑analysis

Change in Olfactory Function Following Deep Brain Stimulation: A Systematic Review and Meta‑Analysis

Efficacy and Neuropsychiatric Outcomes of Deep Brain Stimulation in Meige Syndrome: A Meta‑Analysis

Diagnostic Performance of Algorithm-Based Targeting in Deep Brain Stimulation for Parkinson’s Disease: A Systematic Review and Meta-analysis

Effect of Deep Brain Stimulation on Sexual Function in Parkinson’s Disease: A Systematic Review and Meta‑Analysis

Effects of Deep Brain Stimulation on Gait Velocity in Parkinson’s Disease: A Meta‑analysis

Speech and Voice Outcomes Following Subthalamic Versus Pallidal Deep Brain Stimulation for Parkinson Disease

Optimization of deep brain stimulation programming for speech impairment in Parkinson disease

Sacral Neuromodulation and Urinary Outcomes in Parkinson Disease: A Multicenter Propensity-Matched Cohort Study

Sacral Neuromodulation and Urinary Complications in Multiple Sclerosis: A Propensity-Matched Multicenter Cohort Study

RNS in Multifocal Epilepsy After Failed Resection: A Bilateral Depth‑Electrode Approach in Complex Drug-Resistant Epilepsy

Stereo-EEG Guided Radiofrequency Thermocoagulation for Drug-Resistant Temporal Lobe Epilepsy in a Patient with Prior Lobectomy

Sequential Neuromodulation and Adjunctive Fenfluramine Therapy in Drug-Resistant Epilepsy: A Multimodal Treatment Paradigm

Optimization of Anterior Nucleus of the Thalamus Deep Brain Stimulation in Refractory Focal Epilepsy With Persistent Amnesia

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.