218. Genetics and Phenotypes of Late-Onset Neurodegeneration in Neurodevelopmental Disorders

Article type: Narrative Review

Article title: Genetics and Phenotypes of Late-Onset Neurodegeneration in Neurodevelopmental Disorders

Journal: Cureus

Year: 2025

Authors: Jamir Pitton Rissardo, Fatemeh Rashidi, Masoumeh Rashidi, Meryem Bahar, Kimia Kheirandishdoolabi, Ana Leticia Fornari Caprara, Farbood Khademhamzeh, Sogand Ranjbar, Omesh Prathiraja, and Maleesha Jayasinghe

E-mail: jamirrissardo@gmail.com

ABSTRACT

Late-onset neurodegenerative diseases may originate from subtle vulnerabilities established during early development, yet the specific mechanisms linking early-life factors to later pathology remain poorly understood. Emerging evidence suggests that prenatal and postnatal influences, including genetic predispositions, maternal health, and environmental exposures, shape neural circuits in ways that may predispose individuals to neurodegeneration. Subclinical abnormalities in synaptic pruning, neurogenesis, and immune regulation are increasingly recognized as latent risk factors, but their precise contribution to disease onset has not been clearly defined. Advances in biomarker discovery, particularly in proteomic, genetic, and imaging domains, offer promising opportunities to detect such vulnerabilities before clinical symptoms arise. Despite these insights, the field lacks longitudinal and mechanistic studies that connect early developmental disruptions to specific neurodegenerative outcomes. Addressing this gap will require integrative research that combines experimental models with life-course studies to clarify causal pathways. By identifying concrete mechanistic links, future work may inform more targeted preventive strategies, rather than broadly proposing reductions in global disease burden.

Keywords: early developmental phenotype; genetic predisposition; mitochondrial dysfunction; neurodegeneration; neurodevelopmental disorders.

Full text available at:

https://www.cureus.com/articles/409023-genetics-and-phenotypes-of-late-onset-neurodegeneration-in-neurodevelopmental-disorders#!/

DOI

https://doi.org/10.7759/cureus.93530

Citation

Pitton Rissardo J, Rashidi F, Rashidi M, Bahar M, Kheirandishdoolabi K, Fornari Caprara AL, Khademhamzeh F, Ranjbar S, Prathiraja O, Jayasinghe M. Genetics and Phenotypes of Late-Onset Neurodegeneration in Neurodevelopmental Disorders. Cureus 2025;17: e93530. doi:10.7759/cureus.93530

Figure 1. Late-onset neurodegeneration in neurodevelopmental disorders.

Table 1. Early-onset Parkinson's disease in subjects with PPP2R5D mutation.

Abstract - Fecal Microbiota Transplantation in Patients with Parkinson’s Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials (P11-5.014)

Title: Fecal Microbiota Transplantation in Patients with Parkinson’s Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials (P11-5.014)

Authors: Sania Aimen, Hassan Waseem, Zain Abideen, Jamir Pitton Rissardo, Muhammad Abdullah Ali, Ana Leticia Fornari Caprara, Vishnu Byroju, and Umama Alam

Conference: 2025 AAN Annual Meeting, San Diego, CA

Objective

This meta-analysis assesses the therapeutic effectiveness of fecal microbiota transplantation (FMT) in Parkinson’s disease (PD), synthesizing existing evidence to guide future therapeutic approaches.

Background

PD, a neurodegenerative disorder with motor and non-motor symptoms, is linked to the gut microbiome. FMT can modify gut bacteria, but its effectiveness in PD remains uncertain.

Design/Methods

PubMed, Embase, and Cochrane Library were searched up to September 2024. Risk Ratios (RR) and Mean difference (MD) were pooled for dichotomous and continuous outcomes using Review Manager version 5.4.1. Primary outcomes were changes in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I and II. Secondary outcomes included MDS-UPDRS Parts III (on and off medication) and IV, Irritable Bowel Severity Scoring System (IBS-SSS), Parkinson’s disease Questionnaire-39 Summary Index (PDQ-39 SI), Montreal Cognitive Assessment (MoCA) scores, and gastrointestinal (GI) adverse events.

Results

Three randomized trials pooling 145 PD patients were included in the analysis. FMT and placebo are comparable regarding MDS-UPDRS Part I (MD= −0.36; 95% CI:[−2.18,1.45]; p=0.70; I2=33%), Part II (MD=−0.46; 95% CI:[−1.91,0.99]; p=0.53; I2=0%), Part III (MD=1.41; 95% CI:[−2.14,4.42]; p=0.50; I2=17%), Part III off medication (MD=1.26; 95% CI:[−2.27,4.79]; p=0.48; I2=0%), and Part IV (MD= −0.39; 95% CI:[−1.63,0.85]; p=0.54; I2=24%). No significant changes were observed in IBS-SSS (MD=−15.91; 95% CI: [−63.17,31.89]; p=0.51; I2=76%), PDQ-39 SI (MD=−2.13, 95% CI:[−5.62,1.36]; p=0.23; I2=0%), and MoCA scores (MD=0.11; 95% CI: [−1.34,1.57]; p=0.88; I2=68%). However, gastrointestinal adverse events were more frequent in the FMT group (RR=3.32; 95% CI: [1.01,10.87]; p=0.05; I2=39%).

Conclusions

FMT showed no significant therapeutic effect on motor and non-motor symptoms of Parkinson’s disease compared to placebo, including no notable improvement in cognitive or gastrointestinal outcomes. However, it was associated with a higher frequency of gastrointestinal adverse events. Further research is needed to explore its potential therapeutic role in Parkinson’s disease.

Citation

Aimen S, Waseem H, Abideen Z, Rissardo JP, Ali MA, Caprara AL, Byroju V, Alam U. Fecal Microbiota Transplantation in Patients with Parkinson’s Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials (P11-5.014). Neurology 2025;104(7_Supplement_1):4931.

Figure. Forest plots of the effect of fecal microbiota transplantaion on UPDRS-I, UPDRS-II, UPDRS-III, and UPDRS-IV in patients with PD.

Abstract - Transcutaneous Vagus Nerve Stimulation for Gait and Motor Function in Parkinson’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Title: Transcutaneous Vagus Nerve Stimulation for Gait and Motor Function in Parkinson’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Authors: Jamir Pitton Rissardo and Ana Leticia Fornari Caprara

Conference: 2025 International Congress of Parkinson's Disease, Honolulu, HI

Objective: To evaluate the effects of transcutaneous vagus nerve stimulation (tVNS) on gait, motor function, and freezing of gait (FOG) in patients with Parkinson’s disease (PD).

Background: Gait disturbances and FOG are significant contributors to mobility impairment and fall risk in PD. Non-invasive neuromodulation approaches, such as transcutaneous auricular (taVNS) and cervical (tcVNS) vagus nerve stimulation, have been investigated as potential therapeutic options. However, their impact on motor performance and gait parameters remains unclear.

Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Randomized controlled trials (RCTs) evaluating the effects of tVNS compared to sham stimulation in PD were identified through database searches. Standardized mean differences (SMD) were calculated for key outcomes, including UPDRS-III scores, FOG severity, Timed Up & Go (TUG) performance, step length, stride length, and walking speed. A random-effects model was used to pool effect sizes, and heterogeneity was assessed using the I² statistic.

Results: Four RCTs (PMID: 30889295, 37554394, 37311693, 38925314) met the inclusion criteria, comprising a total of 82 patients receiving tVNS and 74 receiving sham stimulation. tVNS led to improvements in several gait and motor function parameters. Step length significantly increased in the active stimulation group (SMD: 31 ± 58.58), while UPDRS-III scores showed improvements with auricular stimulation (SMD: -4.82 ± 2.35 and -2.87 ± 3.00). FOG severity demonstrated a moderate reduction (SMD: 0.7 ± 0.61), and mobility, assessed by the Timed Up & Go (TUG) test, improved with stimulation (SMD: -0.5 ± 1.32). Walking speed increased (SMD: 0.32 ± 0.07), along with step length (SMD: 13.67 ± 3.91) and stride length (SMD: 28.32 ± 8.1).

Conclusions: tVNS demonstrated modest to moderate improvements in gait, motor function, and FOG severity in PD patients. Both auricular and cervical stimulation showed potential benefits, but variability in effect sizes highlights the need for larger, well-controlled trials to confirm efficacy, determine long-term benefits, and optimize stimulation protocols for gait dysfunction in PD.

Citation

Pending

Figure. Forest and Baujat plots of transcutaneous vagus nerve stimulation on UPDRS-III in patients with Parkinson’s Disease.

Abstract - Repetitive Transcranial Magnetic Stimulation For Freezing Of Gait And Motor Function In Parkinson’s Disease: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials

Title: Repetitive Transcranial Magnetic Stimulation For Freezing Of Gait And Motor Function In Parkinson’s Disease: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials

Authors: Jamir Pitton Rissardo and Ana Leticia Fornari Caprara

Conference: 2025 International Congress of Parkinson's Disease, Honolulu, HI

Objective

To evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on motor function, freezing of gait (FOG), and mobility in patients with Parkinson’s disease (PD).

Background

Freezing of gait and mobility impairments are common and disabling symptoms in PD. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential non-invasive neuromodulatory therapy targeting motor and gait-related circuits. However, the efficacy of different rTMS frequencies and protocols in improving motor symptoms and gait function remains uncertain.

Methods

A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized controlled trials (RCTs) investigating rTMS in PD patients were identified through the PubMed database. Outcomes assessed included changes in the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III), Freezing of Gait Questionnaire (FOG-Q), Timed Up & Go (TUG) test, and walking speed. Standardized mean differences (SMD) and mean differences with 95% confidence intervals (CI) were analyzed using a random-effects model.

Results

Five RCTs (PMID: 33314545, 34102418, 31275542, 31689588, 23516319) met the inclusion criteria, encompassing a total of 140 patients receiving rTMS and 116 receiving sham stimulation. Across studies, rTMS demonstrated varying effects based on stimulation frequency. Continuous theta burst stimulation (cTBS) produced the greatest improvement in motor function, with a mean difference in UPDRS-III scores of -8.50 (95% CI: -9.74, -7.26). High-frequency rTMS showed moderate effects on UPDRS-III (-4.40 to -3.35), while low-frequency stimulation demonstrated less consistent improvements (-5.47 to -1.50). FOG-Q scores showed a trend toward improvement, with reductions of -3.09 (95% CI: -8.15, 1.97) and -2.77 (95% CI: -6.15, 0.61) in studies using low- and high-frequency rTMS, respectively. TUG test performance improved following high-frequency rTMS (mean difference: -3.33 seconds, 95% CI: -5.45, -1.21), while walking speed changes were variable (range: 0.37 to 0.49 m/s improvement).

Conclusions

rTMS, particularly continuous theta burst and high-frequency stimulation, demonstrated moderate improvements in motor function and mobility in PD patients. Effects on freezing of gait were less consistent, suggesting the need for further research to optimize stimulation parameters and identify responders.

Citation

Pending

Figure. Forest and Baujat plots of the effect of repetitive magnetic stimulation on UPDRS-III in Parkinson's disease.

Abstract - Effect of Probiotics on Oxidative, Cognitive and Metabolic Outcomes in Alzheimer’s Disease: A Systematic Review and Meta-analysis of Randomized Clinical Trials (P12-3.014)

Title: Effect of Probiotics on Oxidative, Cognitive and Metabolic Outcomes in Alzheimer’s Disease: A Systematic Review and Meta-analysis of Randomized Clinical Trials (P12-3.014)

Authors: Abdul Hannan Siddiqui, Hassan Waseem, Jamir Pitton Rissardo, Zain Abideen, Ana Leticia Fornari Caprara, Vishnu Byroju, FNU Maria, Saba Yaqoob, Zulfiqar Jogezai, Muhammad Moosa, Asma Saif, Muhammad Bilal, Fizza Batool, Areeba Ehsan, Muhammad Shoaib, and Sania Aimen

Conference: 2025 AAN Annual Meeting, San Diego, CA

Objective

This study aims to analyze the probiotic’s effect on neurocognitive function and markers of oxidative stress in Alzheimer’s disease (AD) patients.

Background

AD, being a progressive neurodegenerative disease, constitutes nearly 70% of all the cases related to dementia. Different oxidative stress reduction therapies are being discussed for AD including probiotics.

Design/Methods

PubMed, Cochrane Central, and ScienceDirect were searched till September 2024. The cognitive outcome of interest was the Mini-Mental State Examination (MMSE) score while the metabolic and oxidative outcomes of interest were levels of glutathione (GSH), nitric oxide (NO), malondialdehyde (MAD), total antioxidant capacity (TAC), homeostatic model of assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), triglycerides (TAG) and total cholesterol. Statistical analysis was performed on Review Manager version 5.4.1 employing a random effects model. The Cochrane RoB 2.0 tool was used for quality assessment.

Results

Five randomized clinical trials were included in the final analysis. The results depict that the MMSE score (MD = 2.49; 95% CI: [0.44,4.53] ; p = 0.02; I2 = 85%) and GSH levels (MD = 17.78 μmol/L, 95% CI: [3.07,32.50]; p=0.02; I2=0%) were significantly higher in the probiotics group. Probiotics also resulted in reduced MAD (MD = −1.54 μmol/L, 95% CI;[−2.31,−0.78] ; p<0.0001; I2 =95%), HOMA-IR (MD =−0.30, 95% CI:[−0.55,−0.05]; p=0.02; I2 =0%) and an increase in QUICKI (MD =0.01, 95% CI:[0.00,0.01]; p=0.03; I2 =0%) levels compared to placebo. Other outcomes like TAC (MD =−0.80 mmol/L, 95% CI:[−101.78,100.19]; p=0.99; I2 =84%), NO (MD =−0.64 μmol/L, 95% CI:[−2.92,1.63]; p=0.58; I2 =31%), TAG (MD =−14.55 mg/dL, 95% CI:[−30.73,1.63]; p=0.08; I2 =0%), total cholesterol (MD =−3.98 mg/dL, 95% CI:[−15.68,7.71]; p=0.50; I2 =0%) were comparable between two groups.

Conclusions

Probiotics improved neurocognitive function in AD patients. They also increased antioxidants like GSH, reduced inflammatory markers like MAD, and lowered insulin resistance.

Citation

Siddiqui AH, Waseem H, Rissardo JP, Abideen Z, Caprara AL, Byroju V, Maria FN, Yaqoob S, Jogezai Z, Moosa M, Saif A. Effect of Probiotics on Oxidative, Cognitive and Metabolic Outcomes in Alzheimer’s Disease: A Systematic Review and Meta-analysis of Randomized Clinical Trials (P12-3.014). Neurology 2025;104(7_Supplement_1):48. doi: 10.1212/WNL.0000000000208368.

Figure. Forest plots showing the effect of probiotics on oMMSE, glutathione, and malondialdehyde in patients with Alzheimer's disease.

Abstract - Demographic Trends in Status Epilepticus-Related Morality in Older Adults in the United States (1999–2020): A Nationwide Retrospective Analysis (P12-9.013)

Title: Demographic Trends in Status Epilepticus-Related Morality in Older Adults in the United States (1999–2020): A Nationwide Retrospective Analysis (P12-9.013)

Authors: Zain abideen, Hassan Waseem, Jamir Pitton Rissardo, Sania Aimen, Ana Leticia Fornari Caprara, and Vishnu Byroju

Conference: 2025 AAN Annual Meeting, San Diego, CA

Objective

This study aims to study the demographic trends in status epilepticus-related mortality in older adults (≥65) in the United States from 1999 to 2020.

Background

Status epilepticus (SE) is a neurological emergency characterized by prolonged or recurrent seizures, often associated with significant morbidity and mortality. Despite advances in treatment, SE-related mortality remains high, particularly in older patients with underlying health conditions.

Design/Methods

Death certificate data from the CDC WONDER database was analyzed using the Multiple-cause of death MCD-ICD 10 codes (G41.0–G41.2, G41.8, G41.9) for patients ≥ 65 years. Age-adjusted mortality rates (AAMRs) per 100,000 and Annual percentage changes (APCs) along with 95% CIs were calculated using the Joinpoint Regression Program and stratified by age, gender, race/ethnicity, census region, and state.

Results

There were 17,883 SE-related deaths in older adults from 1999–2020. The AAMR declined from 1.5 in 1999 to 1.2 in 2005 (APC= −4.56, 95 %CI: −8.05, −0.94) after which it inclined to 3.3 in 2020 (APC=7.72, 95% CI: 7.04, 8.41). Women had a consistently higher AAMR than men from 1999 (AAMR women:1.5 vs men:1.4) to 2020 (AAMR women: 3.4 vs men: 3). Non-Hispanic (NH) black had the highest AAMR (5.1), followed by NH Indian or Alaska Native (2.9), NH white (1.9) and Hispanics or Latinos (1.8). Mortality also varied substantially by Census region with the highest AAMR in the south region (2.2), and state with the District of Columbia having the highest (4.2) and Nebraska having the lowest (1.0) AAMRs. According to the place of death medical facilities observed the highest percentage (83.8%).

Conclusions

SE-related mortality increased from 1999–2020. Substantial gender and racial disparities were also observed with women exhibiting a consistently higher mortality than men and NH blacks having the highest mortality. Further studies and targeted interventions are required to address these disparities.

Citation

Abideen Z, Waseem H, Rissardo JP, Aimen S, Caprara AL, Byroju V. Demographic Trends in Status Epilepticus-Related Morality in Older Adults in the United States (1999–2020): A Nationwide Retrospective Analysis (P12-9.013). Neurology 2025;104(7_Supplement_1):5635. doi: 10.1212/WNL.0000000000212491

Figure. Trends in status epilepticus-related mortality in older adults in the United States (1999–2020).

Abstract - Demographic Trends in Primary Malignant Brain Tumour-related Mortality in Older Adults in the United States (1999–2020): A Retrospective Analysis (P10-6.015)

Title: Demographic Trends in Primary Malignant Brain Tumour-related Mortality in Older Adults in the United States (1999–2020): A Retrospective Analysis (P10-6.015)

Authors: Omar Elmandouh, Hassan Waseem, Zain Abideen, Jamir Pitton Rissardo, Sania Aimen, Ana Leticia Fornari Caprara, and Vishnu Byroju

Conference: 2025 AAN Annual Meeting, San Diego, CA

Objective

We aim to study the demographic trends in malignant brain tumor (MBT)-related morality in adults (≥55) in the United Scale from 1999–2020.

Background

Malignant primary brain tumors are aggressive cancers originating in the brain. These tumors have a high mortality rate due to their location, rapid growth, and limited treatment options. Over the past few decades, there has been little improvement in survival rates, and mortality trends for these tumors have remained consistently high.

Design/Methods

Mortality data was abstracted from the CDC WONDER database and analyzed using the multiple-cause of death MCD-ICD 10 code (C71.0–C71.9). Age-adjusted mortality rates (AAMRs)/100,000 and Annual percentage changes (APCs) along with 95% CI were calculated using the Joinpoint regression and stratified by the age, gender, race, census region, state, and location of death.

Results

A total of 242,294 primary MBT-related deaths occurred in older adults in the United States from 1999–2020. The overall AAMR declined from 15.3 in 1999 to 13.8 in 2006 (APC = −0.84, 95% CI:−1.49, −0.17), this was followed by a steep incline to 15.4 in 2020 (APC=0.55, 95% CI: 0.39, 0.70). Men exhibited a consistently higher AAMR than women from 1999 (AAMR men: 18.8 vs women: 12.6) to 2020 (AAMR men: 18.8 vs women: 12.6). When stratified by race Non-Hispanic (NH) white showed the highest AAMR (16.4) followed by Hispanics (10.1), NH black (8.5) and American Indian (7.4). Among the Census regions, Midwest had the highest AAMR (15.2), while South Dakota showed the highest state-level AAMR (18.4).

Conclusions

The study shows a decline in malignant brain tumour (MBT)-related mortality from 1999 to 2006, followed by an increase through 2020, with men and non-Hispanic whites having the highest mortality rates.

Citation

Elmandouh O, Waseem H, Abideen Z, Rissardo JP, Aimen S, Caprara AL, Byroju V. Demographic Trends in Primary Malignant Brain Tumour-related Mortality in Older Adults in the United States (1999–2020): A Retrospective Analysis (P10-6.015). Neurology 2025;104(7_Supplement_1):5972). doi: 10.1212/WNL.0000000000212707

Figure. Trends in primary malignant brain tumor-related mortality in older adults in the United States (1999–2020).

Abstract - Comparing Burr-Hole Drainage with or Without Irrigation in Chronic Subdural Hematoma Patients: A Systematic Review and Meta-Analysis (P10-14.011)

Title: Comparing Burr-Hole Drainage with or Without Irrigation in Chronic Subdural Hematoma Patients: A Systematic Review and Meta-Analysis (P10-14.011)

Authors: Muhammad Fawad Tahir, Hassan Waseem, Jamir Pitton Rissardo, Zain abideen, Sania Aimen, Ana Leticia Fornari Caprara, Vishnu Byroju, Khadija Ahmed, Maimoona Khan, Sami Ullah Khan, and Muhammad Ahmed Ayaz

Conference: 2025 AAN Annual Meeting, San Diego, CA

Objective

To assess the efficacy and safety of irrigation during burr hole drainage for chronic subdural hematoma.

Background

The commonly used method for treatment of chronic subdural hematoma is burr hole craniotomy. However, the therapeutic effects of irrigation used during this method are still not well understood.

Design/Methods

PubMed, Cochrane Central, and ScienceDirect were searched till September 2024. The primary and secondary outcomes of interest were the recurrence rate of subdural hematoma, mortality, post-operative infections, hemorrhagic complications, and pneumocephalus. Risk ratios (RR) along with 95% CIs were calculated for categorical outcomes using the Review Manager Software 5.4.1 and employing a random effects model. The quality of the included studies was evaluated using the Newcastle Ottawa scale and Cochrane RoB 2.0 tool. A leave-one-out sensitivity analysis was performed to investigate the source of heterogeneity. The risk of publication bias was assessed through funnel plots and Eggers’s regression test.

Results

Fourteen studies were included in the final analysis with a total of 2,251 patients. There was no significant difference in the recurrence rate of subdural hematoma (RR=1.01; 95% CI: [0.64, 1.61]; p =0.95; I2=54%) and mortality (RR=1.13; 95% CI: [0.69, 1.84]; p =0.63; I2=0%) between the two groups. Similarly, no statistically significant difference was observed in the risk of postoperative infections (RR=0.87; 95% CI; [0.51, 1.47]; p=0.60; I2=0%), hemorrhagic complications (RR=1.35; 95% CI: [0.30, 6.05]; p=0.69; I2=63%) and pneumocephalus (RR=2.56; 95% CI: [0.95, 6.89]; p=0.06; I2=82%) between the irrigation and no irrigation groups.

Conclusions

In conclusion, burr hole craniotomy with or without irrigation shows comparable safety and efficacy outcomes. Further high-quality multicenter randomized clinical trials are required to confirm if irrigation has effects in improving the efficacy outcomes or reducing complications for better applicability in clinical practice.

Citation

Tahir MF, Waseem H, Rissardo JP, abideen Z, Aimen S, Caprara AL, Byroju V, Ahmed K, Khan M, Khan SU, Ayaz MA. Comparing Burr-Hole Drainage with or Without Irrigation in Chronic Subdural Hematoma Patients: A Systematic Review and Meta-Analysis (P10-14.011). Neurology 2025;104(7_Supplement_1):4733). doi: 10.1212/WNL.0000000000211877

Figure. Forest plots of the hematoma recurrence and all-cause mortality of burr-hole drainage with or without irrigation in chronic subdural hematoma.

Abstract - Incidence of Somatosensory Aura in Epilepsy: A Systematic Review (P10-9.005)

Title: Incidence of Somatosensory Aura in Epilepsy: A Systematic Review (P10-9.005)

Authors: Aswathi Sajeendran, Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, and Vishnu Byroju

Conference: 2025 AAN Annual Meeting, San Diego, CA

Objective

To systematically investigate the incidence of somatosensory aura (SSAs) in epilepsy.

Background

SSAs are characterized by abnormal sensations on one or more body parts that may spread following a somatotopic pattern.

Design/Methods

Six databases were used to find the studies in electronic form about somatosensory auras in epilepsy, published until June 2024. Science Direct, Embase, Lilacs, Google Scholar, PubMed, and Scielo were searched. The terms used for the search were “somatosensory, aura, epilepsy.” There was no language restriction. Studies including the incidence of SSAs during one year were included, and the data was adjusted according to sample size.

Results

20 studies containing 12927 patients with epilepsy were found. 695 patients developed at least one episode of SSAs in a period of one year. The incidence of SSAs was 5.38% (538 had SSAs for every 10000 individuals with epilepsy) during a period of one year. The occurrence of SSAs among individuals with epilepsy ranged from 1.42% to 80%. The upper extremities are more commonly affected in SSAs, followed by the lower extremities and the face. The most common type of SSAs is paresthetic, followed by painful and thermal auras. In the primary SSAs, sensations occur more commonly contralaterally, while the secondary SSAs can be ipsilateral or bilateral. Despite the high localizing features of SSAs, cortical stimulation studies have shown overlapping sensations originating in the insula and the supplementary sensorimotor area.

Conclusions

There was a wide variability in the incidence of SSAs in the studies from the literature. Some of the epilepsy mimics that should be considered in patients with SSAs are Alice-in-Wonderland syndrome, psychogenic non-epileptic paroxysmal events, syncope, migraine, and cerebrovascular non-epileptic paroxysmal events.

Citations

Sajeendran A, Caprara AL, Rissardo JP, Byroju V. Incidence of Somatosensory Aura in Epilepsy: A Systematic Review (P10-9.005). Neurology 2025;104(7_Supplement_1):3126. doi: 10.1212/WNL.0000000000210812

Table. Incidence of Somatosensory Aura in Epilepsy.

Abstract - Tumor Embolic Stroke and Endovascular Thrombectomy: A Literature Review

Title: Tumor Embolic Stroke and Endovascular Thrombectomy: A Literature Review (P8-13.012)

Authors: Vishnu Byroju, Jamir Pitton Rissardo, and Ana Leticia Fornari Caprara

Conference: 2025 AAN Annual Meeting, San Diego, CA

Objective

To review the literature on tumor embolic stroke (TES) undergoing endovascular thrombectomy (EVT).

Background

Although it is well recognized, the literature regarding EVT in TES is scarce. Some studies have found a high risk of intracranial hemorrhage (ICH) after thrombolysis in patients with cancer-related stroke (CRS).

Design/Methods

The PubMed (Medline) database was used to find the studies in electronic form about EVT in TES published to June 2024. The search terms to use for the search were “tumor, stroke, and thrombectomy.” There was no language restriction. The initial search obtained 177 studies, from which 50 were selected. Only fragment or entire tumor dislodgement resulting in a stroke, which is a subset of CRS, was included.

Results

The median age was 45.8, female subjects comprised 15 out of 50, gender was not reported in 2 and the rest were male. 7/50 were pediatric cases with age <21. 1 case reported adverse outcomes, the rest did not have complications from EVT. Deaths reported later in the hospital course were primarily attributable to complications from underlying malignancy or respiratory failure. 24/50 TES were secondary to myxoma. Several other tumors, including but not limited to cardiac papillary fibroelastomas, amorphous tumors, sarcomas, and renal cell carcinomas, resulted in TES. The rate of ICH in TES is comparable to that of patients without active malignancy (5–10% in both groups).

Conclusions

A literature review suggests EVT is safe in TES, and novel techniques improve outcomes. The rate of ICH in patients undergoing EVT for stroke is similar in patients with and without cancer. EVT demonstrates safety in TES. Several novel techniques of EVT demonstrate safety and efficacy in treating TES; in certain cases, outcomes are superior to medical management alone.

Citation

Byroju V, Rissardo JP, Caprara AL. Tumor Embolic Stroke and Endovascular Thrombectomy: A Literature Review (P8-13.012). Neurology 2025;104(7_Supplement_1):3124). doi: 10.1212/WNL.0000000000210810

Figure. Incidence, localization, and outcomes of tumor embolic stroke (TES). The top panel presents the distribution of tumor types implicated in TES, with cardiac myxoma comprising the largest proportion (47%), followed by sarcomatoid carcinoma (26%), papillary fibroelastoma (16%), and smaller contributions from lung malignancy (5%), metastatic melanoma (2%), phyllodes breast tumor (2%), and cardiac sarcoma (2%). The lower left panel summarizes outcomes following endovascular therapy (EVT), showing favorable results in 47% of cases, poor outcomes in 13%, favorable outcomes with unrelated mortality in another 13%, and unknown outcomes in 27%. The lower right panel maps the vascular territories affected by TES, highlighting occlusions in the right middle cerebral artery (32%), left internal carotid artery (26%), basilar/posterior circulation (26%), and right internal carotid artery (16%).