United States

Objective: This study aims to evaluate recent literature on cancer vaccines, focusing on emerging strategies and advancements in vaccine development. With increasing interest in immunotherapy, novel vaccine delivery mechanisms may enhance efficacy and broaden therapeutic applications.

Methods: A comprehensive literature review analyzing published studies and clinical trial data on cancer vaccines was conducted. Research articles detailing vaccine formulations, immune response mechanisms, and clinical outcomes were included. Particular attention was given to novel approaches, such as nanoparticle-based vaccine delivery.

Results: Recent findings highlight the incorporation of nanoparticles as a promising strategy for cancer vaccine delivery. Nanoparticles enhance antigen presentation, improve immune activation, and enable targeted delivery to tumor-associated antigen-presenting cells. Clinical trials have demonstrated improved vaccine stability and efficacy through nanoparticle-based formulations, suggesting potential advantages over conventional vaccine platforms.

Conclusions: The application of nanoparticle technology in cancer vaccines represents a significant advancement in immunotherapy. These innovations may enhance vaccine efficacy, prolong immune responses, and provide new therapeutic opportunities. Further clinical studies are needed to optimize nanoparticle-based vaccine formulations and assess long-term safety and effectiveness.

2025 AMA Research Challenge – Member Premier Access

Cancer Immunotherapy and Nanoparticles: Enhancing Vaccine Efficacy through Advanced Delivery

Congratulations to all the researchers who have qualified for the AMA Research Challenge virtual poster symposium and semifinals!

Welcome to the **largest national, multi-specialty research event** featuring research from nearly 1,000 medical students, residents, fellows, and international medical graduates across six topic areas - basic science, clinical and translational research, clinical vignettes, health systems science, medical education, and public health and health policy.

#### Access the Event
Use the buttons below or navigation menu to access the event. 

[![](https://assets.underline.io/markdown_image/1/image/d4076f2146939317a29eb9f69c53ad41.png)](https://underline.io/events/506/sessions?searchGroup=all)
[![](https://assets.underline.io/markdown_image/1/image/6bcee0b523a4874c4292ca0415d88dde.png)](https://underline.io/events/506/posters?searchGroup=all)
[![](https://assets.underline.io/markdown_image/1/image/0ca1b933deefd7731529477b45345166.png)](https://underline.io/events/506/schedule)

#### Event Details
The 2025 AMA Research Challenge includes the following symposium halls:
* **Semifinals hall:** Features research from 54 medical students, residents and international medical graduates that received top scores during first round scoring. 
* **Poster symposium hall:** Features research from nearly 1,000 medical students, residents and international medical graduates categorized by topics and subtopics.

**Here’s how to participate:**
* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with presenters** and provide feedback to help advance their research
* **New this year: Watch live poster presentations** by topic area and engage directly with researchers

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge final round, present their research to an elite panel of judges, and compete to win a $10,000 grand prize presented by Laurel Road.

#### A message from Dr. Bobby Mukkamala, AMA President
<div style="position: relative; width: 100%; padding-bottom: 56.25%; height: 0; overflow: hidden;">
  <iframe 
    src="https://underline.io/embed/136894-ama-video?t=0"
    title="AMA Welcome Video"
    allowfullscreen
    style="position: absolute; top: 0; left: 0; width: 100%; height: 100%; border: 0;">
  </iframe>
</div>


#### Recognized Institutions
In 2025, 1,400 abstracts were submitted across six topic areas representing 174 medical schools and more than 150 residency and health care institutions. [See if your institution is represented this year!](https://drive.google.com/file/d/1eFrTqCmCeobx9pr5drJK2hllvsIpFNOY/view?usp=drive_link)

#### Grand Prize Sponsor
AMA would like to thank Laurel Road, a brand of KeyBank, for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road and KeyBank are not involved in winner selection process. The winner will be announced during the AMA Research Challenge final round. Payment of the grand prize will be directly from Laurel Road/KeyBank. See the [AMA Research Challenge Official Rules for terms and conditions](https://www.ama-assn.org/system/files/research-challenge-official-rules.pdf).

[![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)](https://www.laurelroad.com/)

#### Code of Conduct
<html>
AMA has a code of conduct for its meetings – we ask all attendees to adhere to this code to participate in this year’s meeting. Please read and <a href="https://www.ama-assn.org/about/code-conduct" target="_blank">learn more here</a> about your conduct requirements.
<br><br>
	</html>
	

#### Semifinals Judges

You need to log in with the email address you registered with. Access credentials have been sent to your email. 

Please be sure to check your spam and other email folders if you do not see an email confirmation right away.

Need help? Contact us at <support@underline.io>.

Please log in to explore this event.

If you have used the AMA Research Challenge platform previously, please click the ‘Log-in’ button below. If you do not remember your password, please click “forgot password” and follow prompts to reset your password. After resetting your password, please refresh your webpage to access the platform. 

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals. 

**Please use [this link here](https://www.ama-assn.org/member-benefits/events/ama-research-challenge) to register for free. **

Registration Is Required

Join the AMA Research Challenge poster symposium and semifinals to explore top research posters and score posters in the semifinals (an AMA member exclusive opportunity).


The gut microbiome plays a critical role in brain development and function, yet the neural mechanisms underlying microbiome-brain interactions during social processing remain poorly understood. We hypothesized that microbiome depletion fundamentally alters how the brain processes social information across different contexts.


We developed a three-day social context paradigm using FDG-PET neuroimaging in antibiotic-treated (ABX, n=10) and control (CON, n=10) mice. Mice underwent scanning in three contexts: isolation (day 1), familiar social interaction (day 2), and novel social interaction (day 3). Statistical parametric mapping identified brain regions showing significant context-dependent changes in glucose metabolism (p<0.001). ABX mice were administered a broad-spectrum antibiotic cocktail through the drinking water (ampicillin (1 g/L), vancomycin (0.5 g/L), neomycin (1 g/L), and metronidazole (1 g/L) in sterile drinking water), while control mice (CON) received regular drinking water

Microbiome depletion induced distinct context-dependent neural signatures. During transitions from isolation to familiar social contexts, CON mice showed appropriate engagement of social memory circuits (lateral entorhinal cortex, anterior cortical amygdaloid nucleus) with concurrent decreases in primary somatosensory and prelimbic regions. In contrast, ABX mice showed no significant changes between these contexts. When transitioning from isolation to novel social contexts, ABX mice exclusively engaged sensory processing regions (superior colliculus, secondary visual cortex, somatosensory barrel field) without any decreases in regional activity. During familiar-to-novel social transitions, ABX mice further increased sensory processing (visual cortex, somatosensory barrel field), while CON mice showed appropriate motor engagement and decreased somatosensory activity. Notably, ABX mice showed no decreases in neural activity during any context transition.


Microbiome depletion fundamentally alters context-dependent neural processing during social interaction, causing a shift from social memory circuits to compensatory sensory processing. This suggests microbiome-depleted animals maintain social functioning through alternative neural strategies that rely heavily on sensory information rather than appropriate social memory engagement. The absence of neural inhibition during context transitions in microbiome-depleted mice reveals a previously unrecognized mechanism by which microbiome alterations may contribute to social processing deficits in neurodevelopmental and psychiatric conditions.


Compensatory functional connectivity resolves neuro-behavioral dissociation in socially engaged microbiome-depleted mice

Background
Human Respiratory Syncytial Virus (hRSV) is a leading cause of lower respiratory tract infections, particularly affecting infants, older adults, and immunocompromised individuals. The virus exists as two major types, RSV A and RSV B, each with distinct clades that aid in tracking viral evolution. Outbreak timing and severity can differ even within nearby areas, and genetic similarities are often seen across neighboring regions. Ongoing viral evolution poses challenges to long-term vaccine development, underscoring the need for localized genomic surveillance to guide public health efforts. This study analyzed hRSV-positive cases from the Emory Healthcare Microbiology Lab to identify mutations that may impact viral fitness and antigenicity. We summarized the genomic evolution of hRSV during the 2024–2025 season at Emory University Hospital and demonstrated how integrating genomic and clinical data can enhance our understanding of viral adaptation, informing both treatment and vaccine development.

Methods
Residual nasal swabs were collected from 182 hRSV-positive adult patients at Emory University Hospital between September 2024 and March 2025. Nucleic acids were extracted, reverse-transcribed to cDNA, and used to generate multiplex RSV amplicon libraries, which were sequenced using Illumina MiSeq or NextSeq platforms (~2 million reads per sample). Genomes were aligned with MAFFT, clades assigned using Nextclade, and mutations analyzed to track potential immune escape variants.

Results

Among RSV A samples, clades A.D.3.1, A.D.5.2, and A.D.1.5 were most prevalent, while RSV B samples were primarily B.D.E.1, with additional cases of B.D.4.1.1 and B.D.E.1.4. In vaccinated individuals (n = 17), infections involved a genetically diverse mix of strains, with B.D.E.1 (24%), B.D.4.1.1 (18%), and A.D.3.1 (12%) being the most common. No single clade predominated among breakthrough infections. Symptom profiles appeared similar between vaccinated and unvaccinated individuals, with the most notable difference being mortality, which was observed only in unvaccinated patients.

Conclusion
Our analysis revealed that multiple RSV A and B clades co-circulated during the 2024–2025 season, demonstrating substantial viral diversity across the region. Breakthrough infections among vaccinated individuals were linked to a wide range of clades, with no evidence of a single dominant escape variant. While our findings align with broader regional trends, we also identified distinct local variants, reinforcing the importance of continued, localized genomic surveillance. The study was limited by sample size and scope, highlighting the need for expanded surveillance efforts. Ongoing analyses using Nextclade will focus on identifying prevalent escape mutations driving immune evasion. This genetic diversity in both vaccinated and unvaccinated individuals emphasizes the evolving nature of RSV and the need for adaptive public health strategies and vaccine design.


Genomic Epidemiology of Human Respiratory Syncytial Virus in Vaccinated and Unvaccinated Adults in Atlanta, GA (2024-2025)

Background
The Perivascular Fat Attenuation Index (FAI) has emerged as a novel non-invasive biomarker for predicting major adverse cardiovascular events (MACE) and assessing coronary plaque vulnerability. Elevated FAI values are associated with key clinical factors including Type 2 Diabetes Mellitus (T2DM), young age, coronary in-stent restenosis (ISR), stress-related neural activity, non-ST elevation acute coronary syndrome (NSTE-ACS), and high-risk plaque features. This meta-analysis aims to comprehensively evaluate the predictive value of lesion-specific FAI for MACE across these variables, ultimately enhancing cardiovascular risk stratification and clinical decision-making.

Methods
A systematic analysis of studies published between 2018 and 2025 was conducted using PubMed and Embase. Hazard Ratios (HRs) associated with elevated FAI for MACE were collected and compared across high-risk patient subgroups, including individuals with type 2 diabetes mellitus (T2DM), in-stent restenosis (ISR), young adults, stress-related neural activity (NSR), non-ST elevation acute coronary syndrome (NSTE-ACS), high-risk plaque features, and cardiac transplant recipients.

Results
Seven studies (n>6,000 patients) found that elevated lesion specific FAI values were significantly associated with a higher risk of MACE across all subgroups. The CRISP-CT study confirmed these findings, revealing that high-risk plaque features combined with elevated FAI values significantly increased the risk of cardiac mortality (HR = 7.33, p < 0.001). In patients with T2DM, those with lesion-specific FAI values higher than -83.5 Hounsfield Units (HU) exhibited a significantly increased risk of MACE (HR = 2.40, p = 0.001) and a higher prevalence of high-risk plaques. Young patients (≤45 years) with elevated FAI (≥ -75.2 HU) demonstrated a significantly increased risk of MACE (HR = 19.257, p = 0.004). Stress-related neural activity correlated positively with higher FAI values (r = 0.49, p < 0.001), suggesting that stress-induced activation may increase plaque vulnerability. Patients with ISR showed significantly higher peri-stent FAI values compared to those without ISR (-87.2 ± 7.3 HU vs -78.1 ± 6.2 HU, p < 0.001). In the NSTE-ACS and cardiac transplant subgroups, FAI values ≥ -70.1 HU were associated with increased plaque vulnerability and ultimately a higher risk of adverse cardiovascular outcomes. 

Conclusion
Lesion-specific FAI is a unique non-invasive biomarker for predicting MACE in high-risk populations, including T2DM patients, young adults, ISR patients, those with stress-induced neural activity, NSTE-ACS, and cardiac transplant recipients. The strong correlation with high-risk plaque features suggests that FAI can significantly enhance cardiovascular risk stratification and guide personalized intervention strategies. Integrating FAI into clinical practice may improve predictive accuracy and enable more precise and effective management of cardiovascular risk.


The Predictive Value of Perivascular Fat Attenuation Index in Risk
Stratification for Major Adverse Cardiovascular Events

Background
Melanoma is one of the deadliest forms of skin cancer, but it is curable if detected early. Some melanomas closely mimic benign moles (melanocytic nevi), making diagnosis challenging and increasing the risk of diagnostic errors, morbidity, and mortality. Early melanoma originates in the epidermis, the outermost epithelial layer of the skin; however, the role of epidermal keratinocytes in melanoma initiation and progression is not fully understood, leaving their potential as diagnostic or therapeutic targets largely unexplored. To identify key gene signatures of the keratinocyte microenvironment in melanoma progression, we utilized single cell spatial transcriptomics, which enables in-situ gene expression analysis of individual cells while simultaneously accounting for their spatial context within the tumor microenvironment. 

Methods
We used spatial transcriptomics to visualize in situ gene expression of ~6000 genes at a single-cell-level within seven samples: three invasive melanomas, one melanoma in situ, one dysplastic nevus, one common nevus, and one basal cell carcinoma. Multiple fields of view (FOVs) consisting of the epidermal components of both lesional tissue and adjacent non-lesional skin were included from each sample. To visualize cell types and expression patterns across all samples simultaneously, we performed dimensionality reduction and cell clustering using the R package Seurat. Subsequently, the smiDE package was used to perform differential gene expression of keratinocytes, and clusterProfiler was used for Gene Ontology enrichment analysis. 

Results
Our analysis spanned 144 of FOVs, including a total of 147,541 cells across all samples. Cell clustering revealed multiple keratinocyte populations, with some populations more prevalent in malignant samples. In these keratinocytes, the top enriched pathways included keratinocyte differentiation, epidermal proliferation, viral immune response, and wound healing. Initial results discovered 33 upregulated genes within the epidermal keratinocyte microenvironment of melanomas but not nevi, including but not limited to damage associated molecular patterns (DAMPs) S100A7, S100A8, and S100A9, and wound-associated keratins KRT6B and KRT6C. Wound-associated keratins and S100A8/9 were also upregulated in the basal cell carcinoma microenvironment, suggesting that they are associated with both melanocytic and keratinocytic cutaneous malignancies. Additionally, upregulated genes unique to melanomas included DSC2, DYNLL1, LCN2, and RAB11A. 

Conclusion
Our findings identify a keratinocyte population in the tumor microenvironment of melanoma, which exhibits a wound-like proliferative state. Our results build a foundation for identifying biomarkers and therapeutic targets in the epithelial microenvironment of melanoma.

Transcriptionally aberrant keratinocytes shape the tumor microenvironment in melanoma

Background
Reconstructing large segmental tibial defects remains challenging for surgeons. When defects are extensive and involve soft tissue loss, the vascularized free fibular flap (VFFF) offers advantages, including shorter treatment duration and single-site harvest of bone and soft tissue. This study reviews long-term outcomes of VFFF in the reconstruction of segmental tibial defects performed by a single surgeon at our institution.
Methods
The surgical case log of the senior author was reviewed for all adult patients who underwent VFFF reconstruction for tibial defects between 2007 and 2023. Electronic health records were used to collect demographic, clinical, and surgical data, including age, sex, race, comorbidities, etiology of injury, defect size, ankle joint involvement, need for soft tissue coverage, fixation method, and duration of external fixation.
Outcomes included ED visits; unplanned readmissions and reoperations; pin site infections; flap fractures; time to and achievement of full weight-bearing; ambulation without aids; NRS pain scores; time to return to work/avocation; flap success rate; conversion to amputation; and long-term donor/recipient site complications.
Results
Fifteen patients (80% male, mean age 41.4) met inclusion criteria. Most cases resulted from high-energy trauma complicated by nonunion and infection; three cases (20%) involved oncologic resection, and one case involved primary chronic osteomyelitis. The average tibial defect size was 10.91 cm (SD = 2.25), and ankle arthrodesis was performed in 4 patients (27%).
Soft tissue reconstruction was required in 13 patients (87%), with an average defect size of 117 cm² (SD = 40.84). A VFFF skin paddle was used in 11 patients; 3 (20%) required an additional ALT flap. Fixation methods included internal or external fixation, with or without subsequent conversion to a Taylor spatial frame.
The mean number of unplanned reoperations was 1.13. Pin site infections and flap fractures occurred in 3 patients each (20%). Full weight-bearing was achieved in 73% of patients, and 47% were able to ambulate without mobility aids, including orthotic braces. The mean NRS pain score at final follow-up was 1.64 (SD = 2.73), and time to return to work averaged 1.55 years (SD = 1.28). Flap success rate was 93%, with one additional patient electing amputation.
Recipient site complications included lymphedema (N = 3), venous stasis (N = 1), and foot drop (N = 1). Donor site complications included one case of claw toe, which was surgically corrected.
Conclusion
Our study demonstrates that VFFF is an effective option for reconstructing large segmental tibial defects with associated soft tissue loss, achieving an 93% flap success rate and an acceptable complication profile.


Long-Term Outcomes of the Vascularized Free Fibula Flap in the Reconstruction of Large Segmental Tibial Defects: A Retrospective Review

CD38 is an ideal molecular imaging target for multiple myeloma. It is relatively specific for plasma cells and the target of first line therapeutic antibodies, Daratumumab and Isatuximab. Here, we have added a lipid tail to a peptide-based radiotracer that targets CD38 in order to template self-assembly into a polyvalent nanofiber with excellent affinity for CD38. In vitro, the nanofiber outcompetes the monomer for uptake by CD38+ MOLP2 cells. Additionally, these nanofibers can be used to encapsulate and deliver small molecule therapeutics.

CD38-avid Nanofibers for Molecular Imaging of Multiple Myeloma

Abstract: 
Background: 
Primary pulmonary lymphoma (PPL) is a rare form of non-Hodgkin lymphoma (NHL) originating in the lungs, accounting for less than 1% of all NHL cases and under 0.5–1% of primary lung malignancies. Among its subtypes, primary pulmonary follicular lymphoma is particularly uncommon and may present diagnostic challenges due to its nonspecific respiratory symptoms. 
Aim: 
To highlight the clinical presentation, diagnostic workup, and therapeutic approach in a rare case of primary pulmonary follicular lymphoma, with emphasis on bilateral pleural effusion as the initial manifestation. 
Case 
Presentation: 
A 74-year-old male presented with progressive shortness of breath over several weeks without constitutional symptoms or prior pulmonary disease. Imaging revealed bilateral pleural effusions. Initial thoracentesis and cytology were non-diagnostic. Due to worsening symptoms, repeat 
thoracentesis was performed. Flow cytometry and FISH analysis of pleural fluid revealed monoclonal B-cell population positive for lambda CD10, BCL2, BCL6, and t(14;18)/IGH-BCL2 translocation—findings consistent with follicular lymphoma. 
Conclusion: 
This case underscores the importance of considering PPL in the differential diagnosis of unexplained pleural effusions. Despite initial negative cytology, advanced diagnostic tools such as flow cytometry and molecular studies are critical in reaching a definitive diagnosis. Early identification and targeted treatment are essential to optimize patient outcomes in rare presentations of NHL. 


Primary Pulmonary Follicular Lymphoma Presenting with Bilateral Pleural Effusion: A 
Rare Case Report

Introduction
Social determinants of health (SDOH), including socioeconomic status, access to healthcare, and institutional policies, significantly impact the management of chronic conditions such as epilepsy. Financial instability can limit access to essential medications or a medical marijuana card, forcing patients to seek alternative treatments without physician oversight. Patients with limited financial resources often rely on cannabis to manage symptoms, yet institutional regulations and insurance policies create barriers to its use during hospitalization and safe continuation after discharge. This case highlights how a patient’s financial instability, housing situation, and hospital policies on cannabis administration influenced epilepsy management and overall care.

Case Presentation
A 26-year-old male with a history of chronic bipolar disorder, prior traumatic brain injury (TBI) with intracranial hypertension, and epilepsy presented in status epilepticus with incontinence, tongue biting, and postictal confusion. Emergency medical services (EMS) witnessed an additional seizure and administered midazolam en route to the hospital. The patient had a history of medication nonadherence and long-term cannabis use for seizure control. Upon arrival, he had severe metabolic acidosis (ABG: 6.81/38, bicarbonate: 6) and leukocytosis (WBC: 23). He was intubated for airway protection and treated with lorazepam, bicarbonate infusion, and levetiracetam. The patient was admitted to the intensive care unit (ICU) for further management, where he was transitioned to IV valproate sodium and continuous EEG monitoring. His EEG showed encephalopathy, likely influenced by sedation.
Two days later, after extubation and transfer to the neurology unit, the patient expressed a strong desire to leave the hospital, stating that when sober, he became violent. He admitted to daily cannabis use but lacked the financial means to obtain a medical cannabis card. Institutional policies prohibited smoking or self-administering edibles, preventing him from using his preferred method of seizure control. After extensive discussion with hospital administration and the chief medical officer, oral dronabinol was introduced at 2.5 mg up to four times daily as a compromise to ensure his continued hospitalization and neurological evaluation.
The patient was discharged on divalproex but reported severe nausea and vomiting, leading to self-discontinuation after two doses. He had previously discontinued levetiracetam due to mood instability. His epilepsy was strongly influenced by stress, and he cited financial hardship and an unstable living environment as factors worsening his condition. Outpatient MRI showed no acute intracranial abnormalities.
Discussion
This case illustrates how institutional policies can inadvertently create barriers for patients from disadvantaged backgrounds. The patient’s inability to afford a medical cannabis card restricted his ability to self-administer cannabis per hospital guidelines, potentially leading to premature discharge and inadequate seizure management. Hospitals’ restrictive policies on cannabis use, even when legally prescribed, disproportionately impact patients with financial limitations, housing instability, or difficulty accessing traditional pharmaceutical treatments.

Conclusion
Equitable healthcare policies must consider patients' reliance on alternative therapies, like cannabis, particularly for those facing financial or social barriers. Implementing hospital protocols for supervised medical cannabis administration could help mitigate disparities in care, ensuring patients receive comprehensive treatment without disruption due to institutional restrictions.

Rethinking hospital policies that restrict relief in patients who rely on cannabis

The anterior spinal artery (ASA) supplies the vascular distribution to the anterior ⅔ of the spinal cord. This distribution contains many crucial afferent and efferent tracts, including the spinothalamic tracts and corticospinal tracts. Compromise of this tissue can cause extreme morbidity and even mortality. 

Perfusion to neural tissue is the difference between mean arterial pressure (MAP) and intrathecal pressure. The importance of maintaining MAP goals for treating spinal cord ischemia is well documented. However, reducing intrathecal pressure via cerebrospinal fluid (CSF) drainage may also help restore and maintain adequate cord perfusion. CSF diversion is well-documented to improve spinal cord perfusion during aortic surgery, and mounting evidence demonstrates its utility following spinal cord injury. However, there have been very few reports detailing the efficacy of CSF diversion via lumbar drainage in spinal cord ischemia unrelated to aortic surgery or traumatic spinal cord injury.

We describe the use of CSF diversion through a lumbar drain in the treatment of ASA syndrome in a 72-year-old female.


Cerebrospinal Fluid Drainage for the Treatment of Anterior Spinal Artery Syndrome 

Background:
Dysferlinopathy encompasses a group of rare autosomal recessive muscular dystrophies caused by mutations in the DYSF gene, which encodes dysferlin, a protein critical for muscle membrane repair. The main clinical phenotypes include Miyoshi muscular dystrophy and limb-girdle muscular dystrophy type 2B, with a prevalence ranging from 1 in 14,000 to 1 in 2 million individuals. These disorders typically present with progressive proximal and/or distal muscle weakness. No disease-modifying treatments currently exist, and management remains supportive. While certain medications may exacerbate underlying muscle pathology, the interaction between psychiatric medications and genetic myopathies is underrecognized.

Objective: 
To describe a case of dysferlinopathy unmasked and worsened in the setting of atypical antipsychotic therapy, highlighting the importance of considering medication-related muscle toxicity in genetically susceptible individuals.

Case Presentation: 
A 23-year-old male with schizophrenia residing in a psychiatric facility presented with progressive muscle weakness and difficulty ambulating over one year. His symptoms coincided with initiation of monthly paliperidone palmitate. Neurologic examination revealed decreased muscle bulk, bilateral proximal upper extremity weakness (MRC 3/5), proximal lower extremity weakness (MRC 3/5), and hyporeflexia. Laboratory evaluation showed creatine kinase 6,100 U/L, AST 90 U/L, and ALT 150 U/L. Aldolase was within normal range. ANA, ANCA, SSA, SSB, anti-RNP, and anti-Jo antibodies were negative. ESR, CRP, TSH, and T4 were normal. Urinalysis, Hepatitis A/B/C, and HIV tests were negative. Testicular ultrasound and chest X-ray showed no evidence of malignancy. MRI of the lumbar spine demonstrated severe atrophy of the lumbosacral erector spinae muscles. Genetic testing confirmed a pathogenic DYSF mutation, consistent with dysferlinopathy. Muscle biopsy of the right thigh revealed marked fiber size variability, necrosis, regeneration, and increased connective tissue. Paliperidone palmitate was discontinued, and the patient received intravenous methylprednisolone, resulting in significant improvement in muscle strength and reduction of CK levels. He was discharged on aripiprazole and quetiapine with neurology follow-up.

Discussion:
This case highlights the potential for antipsychotic medications, particularly paliperidone palmitate, to exacerbate underlying neuromuscular disorders such as dysferlinopathy. Although antipsychotic-induced myopathy is rare, proposed mechanisms include mitochondrial dysfunction, oxidative stress, and metabolic derangements. The temporal relationship between drug initiation, symptom progression, and improvement following discontinuation supports a drug-induced exacerbation superimposed on a genetic vulnerability. Early recognition and medication adjustment, combined with supportive therapy including corticosteroids, may facilitate meaningful recovery.

Conclusion:
Clinicians should maintain a high index of suspicion for medication-induced worsening in patients presenting with unexplained weakness or elevated CK, particularly those on neuroleptics. This case underscores the need for careful psychopharmacologic management in individuals with known or potential neuromuscular disorders and calls for further research into safe psychiatric treatment strategies for patients with genetic muscle diseases.

Next from 2025 AMA Research Challenge – Member Premier Access

Compensatory functional connectivity resolves neuro-behavioral dissociation in socially engaged microbiome-depleted mice