222. The Role of Vitamin D in Parkinson’s Disease: Evidence from Serum Concentrations, Supplementation, and VDR Gene Polymorphisms

Article type: Systematic Review
Article title: The Role of Vitamin D in Parkinson’s Disease: Evidence from Serum Concentrations, Supplementation, and VDR Gene Polymorphisms

Journal: NeuroSci
Year: 2025
Authors: Jamir Pitton Rissardo and Ana Leticia Fornari Caprara
E-mail: jamirrissardo@gmail.com

ABSTRACT
Background/aim: Vitamin D (VitD) has been implicated in neuroprotection, yet its role in Parkinson’s disease (PD) remains unclear. This systematic review and meta-analysis aimed to evaluate the association between VitD status, supplementation, and vitamin D receptor (VDR) gene polymorphisms with PD risk and outcomes. Methodology: Following PRISMA guidelines, we searched PubMed, Scopus, and Google Scholar through August 2025 for observational studies, clinical trials, and genetic association studies. Primary outcomes included serum VitD levels in PD versus healthy controls (HCs), prevalence of VitD insufficiency/deficiency, and effects of VitD supplementation on motor symptoms. Secondary outcomes assessed associations between VDR polymorphisms and PD susceptibility. Data were synthesized using random- and fixed-effects models, with heterogeneity and publication bias evaluated. PROSPERO (CRD420251133875). Results: Sixty-three studies (n ≈ 10,700 participants) met inclusion criteria. PD patients exhibited significantly lower VitD levels (SMD = −0.46; 95% CI: −0.51 to −0.41) and higher odds of insufficiency (OR = 1.52) and deficiency (OR = 2.20) compared to HC. Cohort data suggested sufficient VitD may reduce PD risk (HR = 0.83). Supplementation yielded modest, non-significant improvements in motor outcomes. Among 20 genetic studies, FokI (rs2228570) was most consistently associated with PD, while other VDR SNPs showed variable or null associations. Conclusions: VitD deficiency is common in PD and may influence disease risk and motor function. Current evidence indicates limited benefit of supplementation for motor outcomes, and genetic associations remain inconsistent.
Keywords: Parkinson’s disease; vitamin D; vitamin D receptor; gene polymorphism; susceptibility.

Full text available at:

DOI

Citation
Rissardo JP, Caprara ALF. The Role of Vitamin D in Parkinson’s Disease: Evidence from Serum Concentrations, Supplementation, and VDR Gene Polymorphisms. NeuroSci 2025;6:130. https://doi.org/10.3390/neurosci6040130
Abstract Figure. Vitamin D and Parkinson’s disease. Abbreviations: HC, healthy control; OR, odds ratio; PD, Parkinson’s disease; SMD, standardized mean deviation; TUG, Timed Up and Go; UPDRS, Unified Parkinson's Disease Rating Scale; UPDRS-III, UPDRS part III; VDR, vitamin D receptor; VitD, vitamin D.

Figure 1. Vitamin D metabolism and receptor (VDR). Abbreviations: Ca, calcium; CUBN, cubilin; DBP, vitamin D binding protein; DHCR7, 7-dehydrocholesterol reductase; hv, light energy; L3, lumisterol 3; LRP2, low-density lipoprotein-related protein 2; MAPK, mitogen-activated protein kinase; NFAT1, nuclear factor of activated T cells; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PDIA3 (ERp57), protein disulfide isomerase family A member 3; PKC, protein kinase C; PLAA, phospholipase A2 activating protein; PLA2, phospholipase A2; RXR, retinoid X receptor; SHH, sonic hedgehog; SRC, steroid receptor coactivator; STAT 1-3, signal transducers and activators of transcription 1 and 3; T3, tachysterol 3; VDR, vitamin D receptor; VDRE, vitamin D response element; WNT, wingless-type MMTV integration site family; △T, temperature change; ↑, increase/upregulate; ↓, decrease/downregulate.
Figure 2. PRISMA flowchart for the identification of included studies.
Figure 3. Forest plots of the vitamin D levels in patients with Parkinson’s disease versus controls.
Figure 4. Forest plots of the vitamin D insufficiency in patients with Parkinson’s disease versus controls.
Figure 5. Forest plots of the vitamin D deficiency in patients with Parkinson’s disease versus controls.
Figure 6. Forest plot of the effect of vitamin D on motor symptoms in patients with Parkinson’s disease compared to healthy controls. TUG, Timed Up and Go test; UPDRS, Unified Parkinson Disease Rating Scale; UPDRS—III, Part III (Motor) of UPDRS.
Figure 7. Forest plots showing odds ratios and 95% confidence intervals for vitamin d-related SNPs in Parkinson’s disease compared with healthy controls under allelic, dominant, recessive, and additive genetic models. Bolded results indicate statistically significant associations with p < 0.05.
Figure 8. Vitamin D in Parkinson’s disease. Abbreviations: AIF, apoptosis-inducing factor; AMPK, adenosine monophosphate-activated protein kinase; BDNF, brain-derived neurotrophic factor; Ca, calcium; Calbindin-D28k, calcium-binding protein that buffers intracellular Ca2+; DA, dopamine; GDNF, glial cell derived neurotrophic factor; GFR⍺1, GDNF family receptor alpha-1; GSH, glutathione; IL4, interleukin 4; IL10, interleukin 10; iNOS, inducible nitric oxide synthase; LC3, microtubule-associated protein 1A/1B-light chain 3; LIF, leukemia inhibitory factor; LPS, lipopolysaccharide; MAO, monoamine oxidase; MAP2, microtubule-associated protein 2; M-CSF, macrophage colony-stimulating factor; NEFH, neurofilament heavy chain; NGF, nerve growth factor; NLRP3, nod-like receptor family, pyrin domain-containing 3; NO2, nitrogen dioxide; nSMase, neutral sphingomyelinase; Nur77, nuclear receptor 77; PARP1, poly(ADP-ribose) polymerase 1; PD, Parkinson’s disease; PI3K, phosphoinositide 3-kinase; ROS, reactive oxygen species; RXRβ/γ, retinoid X receptor isoforms β and γ; SM, sphingomyelin; TGF-β, transforming growth factor-beta; TH, tyrosine hydroxylase; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor alpha; VDR, vitamin D receptor; VEGF, vascular endothelial growth factor; VitD, vitamin D; VMAT2, vesicular monoamine transporter 2; αSyn, α-synuclein; γ-GT, gamma-glutamyltransferase; ↑, increase; ↓, decrease; ↔, no effect, no dependent.
Figure 9. VitD content across selected food sources. * Recommended dietary allowance (1000 IU per day).
Figure 10. Clinical trials assessing the effect of vitamin D on Parkinson’s disease (PD). EEG, electroencephalogram.
Table 1. Summary of associations between VitD and PD risk, symptoms, and genetic factors.
Table 2. Genes roles in dopaminergic neuron function and response to VitD.
Table 3. Vitamin D supplementation summary according to the last guideline by the Endocrine Society.

221. Accepted

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Abstract - Efficacy of Fenfluramine as First-Line Add-On Therapy for Seizure Control in Dravet Syndrome: A Systematic Review and Meta-Analysis

Title: Efficacy of Fenfluramine as First-Line Add-On Therapy for Seizure Control in Dravet Syndrome: A Systematic Review and Meta-Analysis

Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Evren Burakgazi-Dalkilic

Conference: 2025 AES Annual Meeting, Atlanta, GA

Introduction
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by treatment-resistant seizures and high morbidity. Despite the emergence of targeted therapies, first-line management remains challenging. Fenfluramine (FFA), a serotonergic agent with anti-seizure properties, has shown promise as an add-on therapy.

Objective
This systematic review and meta-analysis aimed to evaluate the efficacy of FFA compared to placebo as a first-line add-on treatment in reducing seizure burden among patients with DS.

Methods
A systematic review was conducted according to PRISMA guidelines. Databases were searched for randomized controlled trials (RCTs) assessing FFA versus placebo in DS patients. Studies were eligible if they assessed FFA as a first-line add-on therapy and reported seizure outcomes, including median convulsive seizure frequency (MCSF) and ≥50% and ≥75% responder rates. Risk differences (RD) with 95% confidence intervals (CIs) were extracted or calculated for seizure reduction endpoints. Random-effects meta-analyses were performed using inverse variance methods.

Results
Three treatment arms across two high-quality, double-blind RCTs (PMIDs: 31862249, 31790543) were included, involving a total of 247 patients. FFA doses ranged from 0.2 to 0.7 mg/kg/day. Compared to placebo, the pooled RD for ≥50% reduction in MCSF was –0.18 (95% CI: –0.278 to –0.082), indicating a statistically significant benefit. The RD for ≥75% seizure reduction was –0.14 (95% CI: –0.222 to –0.059), also favoring FFA. The RD for change in median convulsive seizure frequency showed consistent trends but with wider confidence intervals (e.g., RD for 0.7 mg/kg/day: –55.7; 95% CI: –105.6 to 217.0), likely due to heterogeneity in baseline seizure rates. Subgroup analysis by dose suggested greater efficacy at 0.4–0.7 mg/kg/day compared to 0.2 mg/kg/day.

Conclusions
This meta-analysis supports the efficacy of fenfluramine as a first-line add-on therapy in reducing seizure frequency in patients with DS. Clinically meaningful improvements were observed in both ≥50% and ≥75% responder rates. The benefit appeared dose-dependent, with higher doses yielding greater seizure control. These findings support consideration of FFA in early treatment algorithms for DS, although further studies are needed to confirm long-term effectiveness and safety in broader clinical practice.

Citation
Fornari Caprara AL, Pitton Rissardo J, Burakgazi-Dalkilic E. Efficacy of Fenfluramine as First-Line Add-On Therapy for Seizure Control in Dravet Syndrome: A Systematic Review and Meta-Analysis. AES Annual Meeting 2025;2025:146. https://aesnet.org/abstractslisting/efficacy-of-fenfluramine-as-first-line-add-on-therapy-for-seizure-control-in-dravet-syndrome-a-systematic-review-and-meta-analysis

Figure 1. Risk Difference (RD) for Change in Median Convulsive Seizure Frequency (MCSF). Forest plot showing pooled RDs for change in MCSF with fenfluramine versus placebo across included randomized controlled trials. Higher doses (0.4–0.7 mg/kg/day) demonstrated greater efficacy compared to 0.2 mg/kg/day, though confidence intervals were wider due to baseline heterogeneity.
Figure 2. Forest plot of ≥50% responder rate. Meta-analysis of RDs for achieving ≥50% reduction in MCSF with fenfluramine versus placebo. Pooled RD = –0.18 (95% CI: –0.278 to –0.082), favoring fenfluramine.
Figure 3. Forest plot of ≥75% responder rate. Meta-analysis of RDs for achieving ≥75% reduction in MCSF with fenfluramine versus placebo. Pooled RD = –0.14 (95% CI: –0.222 to –0.059), indicating significant benefit of fenfluramine.

220. Alpha-Synuclein Neurobiology in Parkinson’s Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspective

Article type: Narrative Review
Article title: Alpha-Synuclein Neurobiology in Parkinson’s Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives

Journal: Brain Sciences
Year: 2025
Authors: Jamir Pitton Rissardo, Andrew McGarry, Yiwen Shi, Ana Leticia Fornari Caprara, and George T. Kannarkat
E-mail: jamirrissardo@gmail.com

ABSTRACT
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the presence of intracellular α-synuclein (αSyn) aggregates known as Lewy bodies (LB). αSyn, a presynaptic protein, is believed to play a crucial role in synaptic function, neurotransmitter release, and neuronal plasticity. However, its misfolding and aggregation are thought to be central to PD pathogenesis. This review provides a comprehensive analysis of αSyn’s role in PD, exploring its normal physiological functions, pathological mechanisms, and therapeutic potential. The pathological transformation of αSyn involves structural alterations that promote oligomerization and fibrillization, leading to toxic gain-of-function effects. These aggregates disrupt cellular homeostasis through mechanisms including mitochondrial dysfunction, oxidative stress, lysosomal impairment, and endoplasmic reticulum stress. Furthermore, pathogenic αSyn is thought to exacerbate neurodegeneration via prion-like spread along interconnected neuronal circuits. Emerging evidence highlights the frequent co-occurrence of other proteinopathies, such as tau and amyloid-β, which may synergistically accelerate disease progression. Targeting αSyn has emerged as a potential therapeutic strategy. Approaches such as immunotherapy, small-molecule inhibitors, gene silencing, and modulation of protein degradation pathways (e.g., autophagy and proteasomal systems) are actively being explored. Additionally, lifestyle-based interventions, particularly exercise, have shown neuroprotective effects, potentially mediated by irisin—a myokine implicated in protein clearance and synaptic resilience—underscoring the importance of multimodal strategies in PD management.
Keywords: synucleinopathy; co-pathology; neurodegeneration; immunotherapy; biomarkers; prion-like spread.

Full text available at:

DOI

Citation
Pitton Rissardo J, McGarry A, Shi Y, Fornari Caprara AL, Kannarkat GT. Alpha-Synuclein Neurobiology in Parkinson’s Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives. Brain Sci 2025;15:1260. https://doi.org/10.3390/brainsci15121260
Figure 1. Structure of αSyn. In the figure are represented the domains, amino acid sequence, missense mutations, and major post-translational modifications sites of αSyn. Abbreviations: A, acetylation; N, nitration; P, phosphorylation; S, SUMOylation; U, ubiquitination; G, O-GlcNAcylation.
Figure 2. Schematic representation of a neuron highlighting major cellular dysfunctions implicated by pathogenic αSyn. Mutant αSyn promotes misfolding and aggregation into oligomers and fibrils, triggering prion-like propagation across neurons. These aggregates impair synaptic vesicle trafficking and mitochondrial function, disrupt endoplasmic reticulum homeostasis, and interfere with axonal transport. Additionally, αSyn mutations compromise protein clearance mechanisms, including chaperone-mediated autophagy and the ubiquitin–proteasome system, while activating neuroinflammatory cascades through microglial and astrocytic signaling. Collectively, these alterations converge to induce oxidative stress, calcium dysregulation, and neuronal death, highlighting the multifactorial nature of αSyn-driven neurodegeneration.
Figure 3. Schematic representation of proposed αSyn propagation pathways from peripheral organs to the brain. Illustrated are three hypothesized routes by which misfolded αSyn may ascend from peripheral sites to central nervous system structures. Nasal–brain axis: αSyn enters via the olfactory epithelium, propagates through the olfactory bulb and limbic system, and may reach brainstem autonomic centers via multisynaptic connections through the hypothalamus. Kidney–brain axis: aggregates may travel via sympathetic fibers originating in the renal plexus, ascending through the spinal cord to brainstem nuclei. Gut–brain axis: αSyn spreads from the enteric nervous system via the vagus nerve to the dorsal motor nucleus of the vagus (DMV). Arrows indicate proposed directions of propagation.
Figure 4. Tau, amyloid-β, αSyn, and TDP-43 proteinopathies. AD, Alzheimer’s disease; AGD, argyrophilic grain disease; ALS, amyotrophic lateral sclerosis; bvFTD, behavioral variant frontotemporal dementia; CAA, cerebral amyloid angiopathy; CBD, corticobasal degeneration; CJD, Creutzfeldt-Jakob disease; CTE, chronic traumatic encephalopathy; DS, Down syndrome; FFI, fatal familial insomnia; FTLD, frontotemporal lobar degeneration; GVD, granulovacuolar degeneration; GSS, Gerstmann-Sträussler-Scheinker; HD, Huntington’s disease; LATE, limbic-predominant age-related TDP-43 encephalopathy; LBD, Lewy body dementia; MND-TFD, frontotemporal dementia with motor neuron disease; MSA, multiple system atrophy; PD, Parkinson’s disease; PDD, Parkinson’s disease dementia; PiD, Pick’s disease; PSP, progressive supranuclear palsy; sCJD, sporadic Creutzfeldt-Jakob disease; svPPA, semantic variant primary progressive aphasia; VPSPr, variably protease-sensitive prionopathy.
Table 1. Allelic Variants of αSyn in PD.
Table 2. Effect on αSyn and post-translational modifications.
Table 3. Pathological and Motor Phenotypic Characteristics of αSyn Mouse Models.
Table 4. Structural features of αSyn strains.
Table 5. αSyn-Targeted Disease-Modifying Therapies for PD in Clinical Trials Registered in the ClinicalTrials.gov Database.

219. Accepted

Abstract - Unilateral Biportal Endoscopic Discectomy Versus Percutaneous Endoscopic Lumbar Discectomy For Lumbar Disc Herniation: A Systematic Review And Meta-analysis

Title: Unilateral Biportal Endoscopic Discectomy Versus Percutaneous Endoscopic Lumbar Discectomy For Lumbar Disc Herniation: A Systematic Review And Meta-analysis

Authors: Muhammad Hassan Waseem, Zain ul Abideen, Sania Aimen, Justin Chen, Jamir Pitton Rissardo, Brandon Lucke-Wold

Conference: 2025 CNS Annual Meeting, Los Angeles, CA

Introduction
Unilateral biportal endoscopic discectomy (UBED) represents a cutting-edge, minimally invasive approach to treating lumbar disc herniation (LDH). Nonetheless, the effectiveness and safety of UBED in relation to traditional percutaneous endoscopic lumbar discectomy (PELD) have yet to be established.

Objective
This study conducted a meta-analysis to compare UBED with PELD for LDH.

Methods
Relevant cohort studies and clinical trials were found by searching PubMed, Cochrane Central, and ScienceDirect from inception till May 2025. Mean differences (MD) and Risk Ratios (RR) were pooled using the random effects model in Review Manager. Outcomes analyzed were operative time, length of hospitalization, visual analogue scale (VAS) for leg and back, Oswestry disability index (ODI), perioperative complications, and LDH recurrence.

Results
This meta-analysis included 23 studies. Pooled results showed that, compared with PELD, UBED was associated with a longer surgery time (MD = 12.91 min; 95% CI: [7.71, 18.12]; p < 0.00001; I2 = 91%) and hospital stay (MD= 1.21 day; 95%CI:[0.44,1.97]; p=0.002; I2= 95%). However, UBED and PELD showed comparative efficacies in improving the VAS of leg (MD= 0.02; 95%CI:[-0.12,0.17]; p=0.73; I2=21%) and back (MD= 0.09; 95%CI:[-0.07,0.26]; p=0.28; I2= 40%), and Oswestry Disability Index (MD= 0.44; 95%CI:[-1.03,1.90]; p=0.56; I2= 78%), scores. The incidence of perioperative complications was not significantly different between the two techniques (RR= 1.09; 95%CI:[0.74,1.62]; p=0.66; I2= 0%), while UBED was associated with a lower LDH recurrence during follow-up (RR= 0.31; 95%CI:[0.14,0.68]; p=0.003; I2=0%).

Conclusions
While UBED resulted in longer surgery and hospital stays, it demonstrated comparable effectiveness to PELD in relieving pain and improving functional capacity in patients with LDH. Additionally, UBED was associated with a lower recurrence of LDH compared to PELD, with no difference in the rate of perioperative complications. These results support UBED as a viable treatment option for patients with LDH.

Citation
Waseem MH, Abideen Z, Aimen S, Chen J, Pitton Rissardo J, Lucke-Wold B. Unilateral Biportal Endoscopic Discectomy Versus Percutaneous Endoscopic Lumbar Discectomy For Lumbar Disc Herniation: A Systematic Review And Meta-analysis. CNS Annual Meeting 2025;2025:5832. https://www.cns.org/poster-search?id=5832
Figure. Forest plots comparing UBED and PELD for lumbar disc herniation: operative time and length of hospitalization.
Figure. Forest plots comparing UBE and PELD for lumbar disc herniation: Visual Analogue Scale (leg, back) and Oswestry Disability Index outcomes.
Figure. Forest plots comparing UBED and PELD for lumbar disc herniation: perioperative complications and recurrence rates with pooled risk ratios and heterogeneity statistics.

Abstract - Unilateral Biportal Endoscopic Discectomy Versus Microdiscectomy For Lumbar Disc Herniation: A Systematic Review And Meta-analysis

Title: Unilateral Biportal Endoscopic Discectomy Versus Microdiscectomy For Lumbar Disc Herniation: A Systematic Review And Meta-analysis

Authors: Muhammad Hassan Waseem, Zain ul Abideen, Sania Aimen, Justin Chen, Jamir Pitton Rissardo, Brandon Lucke-Wold

Conference: 2025 CNS Annual Meeting, Los Angeles, CA

Introduction
Lumbar disc herniation (LDH) is a prevalent spinal condition that leads to considerable disability, frequently necessitating minimally invasive surgical treatment such as Unilateral biportal endoscopic discectomy (UBED) and Microdiscectomy (MD).

Objective
This study aimed to compare the efficacy and safety of UBED versus MD for the treatment of LDH.

Methods
A literature search was conducted across PubMed, Cochrane Library, and ScienceDirect from inception to May 2025. This study evaluated the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI), MacNab scores, operative time, estimated blood loss, and length of hospitalization at various follow-up durations. The meta-analysis was performed using RevMan 5.4.1 software.

Results
The meta-analysis included 13 studies. The VAS scores for low back pain showed no significant differences between the two groups at postoperative 1–3 months (p = 0.06); however, the UBED group had lower VAS scores at postoperative 1–3 days (MD= -0.81; 95%CI:[-1.48,-0.14];p=0.02; I2= 95%) and 12-months (MD= -0.38; 95%CI:[-0.70,-0.06];p=0.02; I2= 47%). There were no significant differences in leg pain VAS scores at postoperative days 1–3 (p = 0.24), 1–3 months (p = 0.74), or at the 12-month follow-up (p = 0.49). ODI comparisons also revealed no significant differences at the postoperative 1-week (p = 0.47) and 1–3-month (p = 0.21) follow-ups, as well as at the final 12-month follow-up. The UBED group also exhibited a longer mean operative time (MD= 11.12 min; 95%CI:[3.45,18.79];p=0.005; I2= 93%), but significantly shorter hospital stay (MD= -1.47 days; 95%CI:[-2.50,-0.44];p=0.005; I2= 98%) and less estimated blood loss (MD= -74.42 ml; 95%CI:[-114.1,-34.73];p=0.0002; I2= 99%). MacNab scores also showed no significant differences between the two arms (p = 0.10).

Conclusions
The UBED group experienced significantly lower early postoperative pain at 1–3 days and sustained improvement at 12 months compared to MD. Additionally, it showed reduced blood loss and shorter hospital stays along with longer operative times.

Citation
Waseem MH, Abideen Z, Aimen S, Chen J, Pitton Rissardo J, Lucke-Wold B. Unilateral Biportal Endoscopic Discectomy Versus Microdiscectomy For Lumbar Disc Herniation: A Systematic Review And Meta-analysis. CNS Annual Meeting 2025;2025:5719. https://www.cns.org/poster-search?id=5719
Figure. Forest plots comparing VAS back pain scores for UBED vs. MD at 1–3 days, 1–3 months, and 12 months postoperatively.
Figure. Forest plots comparing VAS leg pain scores for UBED vs. MD at 1–3 days, 1–3 months, and 12 months postoperatively.
Figure. Forest plots comparing ODI scores for UBED vs. MD at 1–3 days, 1–3 months, and 12 months postoperatively.
Figure. Forest plots comparing UBED vs. MD for operative time, estimated blood loss, hospitalization length, and MacNab score.

Abstract - Rapid Versus Gradual Weaning of External Ventricular Drain after Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis of Randomized and Non-Randomized Studies

Title: Rapid Versus Gradual Weaning of External Ventricular Drain after Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis of Randomized and Non-Randomized Studies

Authors: Muhammad Hassan Waseem, Zain ul Abideen, Sania Aimen, Justin Chen, Jamir Pitton Rissardo, Brandon Lucke-Wold

Conference: 2025 CNS Annual Meeting, Los Angeles, CA

Introduction
An external ventricular drain (EVD) insertion is among the most frequently performed neurosurgical procedures. It remains unclear whether the weaning method, either gradual or rapid, influences the rate of ventriculoperitoneal shunt (VPS) insertions.

Objectives
This study aims to systematically review the literature comparing gradual and rapid EVD weaning in relation to the VPS insertion rate.

Methods
PubMed, Cochrane Central, and ScienceDirect were searched from inception till May 2025. The Randomized controlled trials and cohort studies comparing gradual and rapid EVD weaning in patients with subarachnoid hemorrhage (SAH) were included in this analysis. The primary outcome was the rate of VPS insertion, while secondary outcomes included the rate of EVD-associated infections and the duration of hospital and ICU stays. The quality assessment was conducted using the Cochrane risk of bias (RoB 2.0) tool and the Newcastle-Ottawa Scale. Publication bias was assessed visually through the funnel plots and statistically through Egger’s regression test.

Results
Five studies, pooling a total of 1,744 patients, were included in this meta-analysis. The VPS insertion rate was low in the rapid EDV weaning, but the results were statistically insignificant (RR = 0.86; 95% CI: [0.59, 1.27]; p = 0.46; I2 = 81%). Similarly, the EVD-associated infections were comparable between the two groups (RR= 0.83;95%CI:[0.50,1.40];p=0.49; I2=51%). However, the length of ICU (MD = -2.94 days; 95% CI: [-3.80, -2.08]; p < 0.00001; I2 = 0%) and hospital (MD = -4.55 days; 95% CI: [-7.14, -1.95]; p = 0.0006; I2 = 62%) stays were significantly shorter in the rapid EVD weaning group.

Conclusions
Rapid EVD weaning was comparable to gradual EVD weaning in terms of VPS insertion rates and EVD-related infections, but it significantly shortens the duration of hospital and ICU stays.

Citation
Waseem MH, Abideen Z, Aimen S, Chen J, Pitton Rissardo J, Lucke-Wold B. Rapid Versus Gradual Weaning of External Ventricular Drain after Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis of Randomized and Non-Randomized Studies. CNS Annual Meeting 2025;2025:6913. https://www.cns.org/poster-search?id=6913
Figure. Forest plot comparing rapid versus gradual external ventricular drain weaning after subarachnoid hemorrhage across randomized and non-randomized studies.

Abstract - Endoscopic Third Ventriculostomy And Choroid Plexus Cauterization Versus Ventriculoperitoneal Shunt In Treatment Of Pediatric Hydrocephalus: A Systematic Review And Meta-analysis

Title: Endoscopic Third Ventriculostomy And Choroid Plexus Cauterization Versus Ventriculoperitoneal Shunt In Treatment Of Pediatric Hydrocephalus: A Systematic Review And Meta-analysis

Authors: Muhammad Hassan Waseem, Zain ul Abideen, Sania Aimen, Justin Chen, Jamir Pitton Rissardo, Brandon Lucke-Wold

Conference: 2025 CNS Annual Meeting, Los Angeles, CA

Introduction
Endoscopic third ventriculostomy with choroid plexus cauterization (EVT/CPC) and ventriculoperitoneal shunt (VPS) are common surgical procedures to treat pediatric hydrocephalus. The combined EVT/CPC has emerged as an effective alternative to VPS. 

Objectives
This study aims to compare the efficacy and safety of combined ETV and CPC with VPS for pediatric hydrocephalus treatment.

Methods
PubMed, ScienceDirect, and the Cochrane Library were searched from inception till October 2024. The PRISMA guidelines were followed. The Risk Ratios (RRs) with 95% Confidence interval (CI) were pooled under the random effects model using the Review Manager 5.4.1 for the dichotomous outcomes. The primary outcome was success rate. Secondary endpoints were postoperative complications, infections, mortality, reoperation, and failure rate. The quality of studies was assessed through the Newcastle Ottawa Scale and the Cochrane RoB 2.0 tool. The Leave-one-out sensitivity analysis was performed to investigate the cause of heterogeneity. Publication bias was assessed visually through funnel plots and statistically through Egger’s regression test.

Results
Eight studies, including 604 patients, were included in this meta-analysis. The success rate was comparable between the ETV/CPC and VPS groups (RR= 0.96; 95%CI: [0.86,1.08]; p=0.53; I2=22%). The postoperative complications rate (RR= 0.67; 95%CI: [0.44,1.03]; p= 0.07; I2=0%) and the failure rate (RR=0.91; 95%CI: [0.48,1.71]; p=0.77; I2=61%) decreased in the EVT/CPC group but the results were statistically insignificant. Other outcomes including infections (RR=0.58; 95%CI:[0.24,1.40]; p=0.23; I2=14%), mortality (RR= 1.14; 95%CI:[0.47,2.73]; p= 0.77; I2= 0%), and reoperation rate (RR= 0.71; 95%CI:[0.14,3.75]; p= 0.69; I2=76%) were also comparable between the 2 arms.

Conclusions
Endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) shows a comparable success rate to ventriculoperitoneal shunt (VPS) in treating pediatric hydrocephalus, with no significant differences in postoperative complications, infections, mortality, or reoperation rates. Despite slight reductions in complications and failure rate with ETV/CPC, these findings were not statistically significant.

Citation
Waseem MH, Abideen Z, Aimen S, Chen J, Pitton Rissardo J, Lucke-Wold B. Endoscopic Third Ventriculostomy And Choroid Plexus Cauterization Versus Ventriculoperitoneal Shunt In Treatment Of Pediatric Hydrocephalus: A Systematic Review And Meta-analysis. CNS Annual Meeting 2025;2025:6585. https://www.cns.org/poster-search?id=6585
Figure. Forest plots comparing ETV+CPC and VP shunt in pediatric hydrocephalus for success rate, postoperative complications, and infection outcomes.
Figure. Forest plots comparing ETV+CPC and VP shunt in pediatric hydrocephalus for mortality, reoperation, and failure rates.
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