United States

Background: Pancreatic ductal adenocarcinoma (PDAC) remains challenging to treat with a 5-year survival rate below 10 %. Its pathogenesis involves a series of genetic events with early stages involving tumorigenesis. Most notably, activation of the K-RAS oncogene and the inactivation of the CDKN2A tumor suppressor have been associated with early-stage development of PDAC. Current chemotherapies are 
often met with therapeutic resistance and fail to target this evolving molecular landscape. To address this gap, systems genetics was employed to construct early-stage PDAC-specific signaling network and identify FDA-approved drugs capable of disrupting key interactions. 
Methods: Expression levels of mRNA for 8 key genes involved in late pathogenesis of 
PDAC — Kras, Cdkn2a, Arid1a, Mll3, Kdm6a, Nr5a2, Clptm1l, and Bcar1—were 
acquired from 193 human pancreas tissues in Gene Network 2.0. Correlations in mRNA expressions were assessed using Pearson correlation matrix. Key signaling pathways were identified via network analysis in NetworkAnalyst 3.0. Protein-protein interaction (PPI) network was constructed using IMEx Interactome database. Functional annotation of PPI network was performed using Gene Ontology (GO) database to identify enriched biological processes, molecular functions, and cellular components. Pharmacogenomic analysis was 
employed to identify FDA-approved drugs with potential to disrupt critical interactions. 
Results: Correlation analysis revealed a strong positive association between Kras and Bcar1, and between Cdkn2a and Arid1a, alongside a significant negative correlation between Cdkn2a and Nr5a2. Protein-protein interaction (PPI) network analysis identified key hub proteins, including YWHAZ, HDAC1, and HDAC2. Functional enrichment of the network highlighted chromatin remodeling and protein ubiquitination as central pathways, underscoring the role of epigenetic regulation and protein degradation in early pathogenesis. Subsequently, pharmacogenomic screening nominated several drugs capable of disrupting critical network interactions, such as Valproic acid (targeting HDAC2), Vorinostat, and Staurosporine.
Conclusion: Correlation matrix analysis demonstrated intricate co-regulatory gene 
network in early-stage PDAC, which drives dysregulation of epigenetic modification and protein degradation pathways, reflecting tumor ecosystem driven by genomic 
instability. Pharmacogenomic analysis identified clinically accessible 
candidates (valproic acid, vorinostat, and staurosporine) targeting multiple proteins within PPI network. Integrating these network-informed agents represents novel precision oncology strategies tailored to the complex biology of early-stage PDAC.

AMA Research Challenge 2025 

Systems Genetics Approach for Repurposing FDA-Approved Drugs against​ Early-stage Human Pancreatic Ductal Adenocarcinoma

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Abstract Title
Platelet-activating factor has a positive effect on intracellular calcium and motility in sea urchin spermatozoa
Background
Platelet-activating factor (PAF) is a pleiotropic phospholipid molecule first described for its role in inflammation, vasodilation, and platelet aggregation. PAF is also known to regulate many different reproductive processes, such as fertilization. Studies have suggested PAF as an autocrine mediator of fertilization via induction of spermatozoa capacitation, a calcium mediated event involving hyperactivation of motility, making it of emergent interest in fundamental reproductive research with fertility applications. While PAF is produced by sea urchin spermatozoa, the mechanism of action of PAF in this organism is uncertain. Therefore, the objective of this study was to determine the effect of exogenous PAF on intracellular calcium and spermatozoa motility in the sea urchin, a time-honored model for developmental physiology studies.
Methods
Spermatozoa shedding from Lytechinus variegatus sea urchins was induced by peri-oral injection of 0.5M KCl. Sperm motility, before and after PAF (10-7 M) exposure, was assessed via a computer-assisted semen analyzer (SQA-V Gold, Medical Electronic Systems). Spermatozoa were tagged with a calcium indicator (5µM Fluo-4), incubated for 1 hour at room temperature, and then centrifuged (1,000xg; 1 minute) to remove excess Fluo-4. To minimize movement, spermatozoa were imaged on poly-L-lysine coated slides. Calcium release was observed before and after PAF (10-7 M) exposure via fluorescence imaging acquired using an epifluorescence microscope (Revolve Echo) with a FITC filter set. Images were analyzed using a custom Python-based workflow with Fluo-4 signal intensity recorded as relative fluorescence units (RFU). Lyso-PAF, the biologically inactive form of PAF, was used as a control. Data were analyzed via paired t-test (Sigma Plot).
Results
There was a significant (p<0.05) rise in spermatozoa motility following the addition of PAF (mean SMI=71) over control (mean SMI=47). There was also a significant difference (p<0.05) in intracellular calcium levels following PAF administration (control 14.57 RFU; PAF 17.77 RFU). Lyso-PAF had no effect on motility or intracellular calcium levels.
Conclusion
This study validates PAF as a positive mediator of spermatozoa motility, most likely via an increase in intracellular calcium. Insight into a potential mechanism by which PAF exerts its effects via intracellular calcium release may lead to identification of cell-surface PAF receptors coupled to Gq protein alpha subunits on spermatozoa of the sea urchin. Additional studies are warranted to further understand the cause-and-effect relationship between PAF and intracellular calcium on spermatozoa motility.

PAF Positively Affects Intracellular Calcium and Motility in Sea Urchin 
Spermatozoa

Background: Hormone receptor-positive (HR+) breast cancer has increased annually since 2005 by at least 0.9% in each female ethnicity group. In contrast, hormone receptor-negative (HR-) breast cancer was stable or declining in incidence over the same period. Clinical trials have demonstrated that near complete estrogen deprivation (NCED) treatment in premenopausal women at high risk for recurrence improves rate of freedom from breast cancer. There is insufficient evidence for how early hypo-estrogenemia by NCED affects cardiovascular health, including aortic stiffening, of premenopausal women with HR+ breast cancer. Underlying cardiovascular disease often falls in exclusion criteria for clinical trials, meaning the true cardiovascular impact of aromatase inhibitor agents may be higher than characterized. Prior studies demonstrated that an oophorectomy in premenopausal women was strongly associated with coronary artery disease. We hypothesize that premenopausal women receiving NCED therapy for HR+ breast cancer have cardiovascular declines that can be identified pre-clinically. We present interim baseline and Year 1 data to begin answering this clinical question.  Methods: 90 premenopausal women with breast cancer (67 HR+, 23 HR-) are being recruited from Duke, Wake Forest, and VCU Cancer Centers. Each participant undergoes adenosine stress cardiovascular magnetic resonance (CMR) imaging at baseline (completion of curative therapy +/- NCED initiation) and annually thereafter for 2 years with annual scans up to 5 years from baseline. CMRs are post-processed offline using Circle CVI42 software using phase contrast imaging maps of the flow velocity of ascending and descending aortas at the main pulmonary artery level. Maximal and minimal area from the ascending and descending aorta were contoured. From these areas, ascending and descending aortic distensibility is calculated using brachial blood pressure. Results: At present, baseline aortic stiffness is well matched between the two study groups, demonstrating a well-matched cohort prior to introduction of NCED therapy in HR+ patients. Enrollment is ongoing and each patient in the study is expected to continue to receive Year 1 and 2 scans. Conclusion: The data will help us identify if cardiovascular consequences of breast cancer treatments are great enough to offset the gains made in breast cancer survival from treatment. This incoming data can characterize the impact of treatment for these tumors to improve treatment delivery and cancer outcomes, minimize treatment-related toxicities, and overcome disparities in this population. We aim to develop predictive models to identify women at highest risk for eventual deficits in myocardial blood flow in premenopausal women treated with NCED for HR+ breast cancer.

Aortic Vascular Stiffness Measures in Cardiac Outcomes with Near Complete Estrogen Deprivation Study

Background
Staphylococcal Scalded Skin Syndrome (SSSS) is a rare exfoliative skin disorder caused by exfoliative toxins from Staphylococcus aureus. While classically associated with pediatric patients, SSSS in adults is rare, with an annual incidence of 0.98 per million. Adult presentations are often severe, particularly in immunocompromised individuals or those with renal insufficiency, due to reduced clearance of circulating toxins. This case highlights an atypical adult presentation of SSSS in a patient with end-stage renal disease (ESRD) on hemodialysis.

Case Presentation
A 62-year-old male with a medical history of ESRD on hemodialysis, diabetes mellitus, and peripheral arterial disease presented to the emergency department for dialysis. He was admitted for bacteremia and peri-incisional erythema at a right lower extremity surgical site. Over several days, the patient developed a widespread rash with blistering and skin sloughing across the back, extremities, and face. He underwent an above-the-knee amputation on day 4 of admission for infection control. Dermatology was consulted on day 6. Examination revealed a Nikolsky-positive, Asboe-Hansen–negative desquamating rash with superficial epidermal sloughing and pigment retention. Mucosal involvement was minimal, and blood cultures were negative. Histopathologic diagnosis was not pursued due to clear clinical presentation, retained pigment, and classic distribution of sloughing. The patient remained afebrile and hemodynamically stable. Treatment included completing a 6-day course of vancomycin, wound care with non-adherent dressings, and emollient therapy.

Discussion
This case demonstrates a rare adult presentation of SSSS in a hemodialysis-dependent patient. The diagnosis was made clinically based on desquamation pattern, superficial split level (retained pigment), lack of mucosal involvement, and negative cultures—differentiating it from Stevens-Johnson Syndrome, pemphigus vulgaris, and TEN-like dermatoses. Adult SSSS often presents without bacteremia, particularly in patients with impaired renal function who lack the capacity to clear exfoliative toxins. Recognition of this rare clinical entity in adults is critical, especially in vulnerable populations. Prompt infection control, supportive care, and wound management are central to recovery. This case reinforces the importance of maintaining a broad differential when approaching positive Nikolsky sign presentations and underscores that SSSS is not limited to pediatric populations.

Separating Skin: A rare case of Staph Scalded Skin Syndrome in an Adult

Background:
Injectable drug use (IDU) is a public health issue in the United States. Xylazine, a veterinary tranquilizer, is found added to illicit fentanyl due to its prolonged sedative effects. Xylazine has also been thought to cause wounds due to its vasoconstriction effects. In this study, we examined the population of these patients at our urban academic center to better identify demographics, wound characteristics, and management strategies.
Methods:
Patients presenting to our institution’s emergency department (ED) from January 2017 to December 2024 with a wound related to xylazine use were retrospectively identified using EMERSE, a full-text EMR search engine. Demographics, comorbidities, social history, and wound characteristics were analyzed. Wound photographs were examined for location, size, and severity. Treatment and operative intervention were reviewed.
Results:
We identified 74 patients with 241 wounds secondary to xylazine use. The mean age was 41.2 years old. Patients were more likely to be female (58.1%) and white (93.2%). The average number of ED visits for wound related complaints was 5.5 (range 1-52) and 52.7% of patients left against medical advice during a visit. The most common comorbidities were hepatitis C (82.4%), hepatitis B (23.0%), endocarditis (23.0%), osteomyelitis (20.3%), and HIV (10.8%). A majority (69.0%) of patients had a psychiatric diagnosis (40% generalized anxiety disorder, 40% major depressive disorder, 9% PTSD). Active IDU was reported in 86.9% and tobacco use in 78.6% of patients. 27% of patients reported being unhoused. The most common wound sites were the anterior lower leg and dorsal forearm. 17.6% of patients had exposed bone or tendon. 41.1% of wounds were less than 1 cm2, 37.3% were between 1 cm2 and 1% total body surface area (TBSA), and 21.6% were >1% TBSA. Plastic or hand surgery was consulted on 43.2% of patients. Most received antibiotics (79.7%) and/or wound care (81.8%). Debridement occurred in 44.0% of patients and 5.4% of patients underwent surgery.
Conclusion:
This study characterizes the largest reported cohort of patients suffering from xylazine-associated wounds. Patients were typically of low socioeconomic status and were more often female and white. They often represented to the ED multiple times, had complex comorbiditie, and required expert consultation. Wounds varied in size, location, and depth but were commonly on extremity extensor surfaces. Treatment primarily included antibiotics and wound care, though debridement and surgery were sometimes required. IDU is common in today’s world, and it is imperative for plastic surgeons to have a treatment algorithm in mind when they are consulted for xylazine-associated wounds.

Xylazine-Associated Wounds: A Primer. What Every Plastic Surgeon Should Know

Background:
Neurofibromatosis type 1 is a rare, autosomal dominant genetic disorder caused by mutations in the NFx1 gene, which codes for neurofibromin. The loss of neurofibromin predisposes NF1 individuals to neurofibromas, such as plexiform neurofibromas. The malignant transformation of plexiform neurofibromas to peripheral nerve sheath tumors has been shown to have worse outcomes. Currently, MRI and FDG-PET scans are used to detect tumors in NF1 patients. However, detecting malignant transformation of NF1-associated plexiform neurofibromas utilizing Gallium Dotatate 68, a radiopharmaceutical agent, has not been reported in the current English literature. We present the first reported case of detecting transformation of NF1-associated neurofibroma to malignant peripheral nerve sheath tumor (MPNST) through the utilization of Gallium Dotatate 68.

Case: 
A 13-year-old male with a history of neurofibromatosis type 1 mutation, confirmed with a truncating mutation (c.8134_8135delAA) in Neurofibromin by genetic testing, was referred to the ENT (ears, nose throat) service for a complicated right retropharyngeal mass causing obstructive sleep apnea. The initial evaluation for sleep apnea by the ENT service showed a large right retropharyngeal mass. Initial follow-up imaging with a Neck MRI scan showed a lobular, well-circumscribed mass centered within the right retropharyngeal space with lateral extension into the carotid space. Subsequent Gallium 68 Dotatate PET/CT scan showed a markedly abnormal tracer uptake in the right retropharyngeal mass with a mild uptake in the right parotid gland, greater than the left. The two scans raised suspicion for malignant transformation of a large neurofibroma in the right retropharynx. The patient underwent ultrasound-guided core needle biopsy of the right retropharyngeal mass. The biopsy confirmed malignant transformation of a benign neurofibroma to malignant peripheral nerve sheath tumor (MPNST). Following the diagnosis of MPNST, the patient underwent oncologic management with chemotherapy and radiation to reduce tumor size prior to resection. Subsequently, the patient was cancer-free for more than two years. Recently, the patient developed multifocal pulmonary and hepatic metastatic disease on follow-up imaging that was confirmed via lung biopsy. The patient is currently undergoing treatment with additional chemotherapy and radiation for recurrent disease.


Discussion:
The Gallium 68 Dotatate PET/CT scan helped to confirm the MRI scan findings and suggested a new, important finding: metastasis to the right parotid gland. This case report demonstrates that Ga-68 Dotatate PET scans can be utilized as an effective alternative for early detection, diagnosis, and metastasis for MPNSTs in NF1 patients. Additional research into the use of Ga-68 Dotatate PET scan in detecting MPNSTs is necessary to determine the sensitivity and specificity of this pharmaceutical agent compared with the standard F18- FDG PET scan. Other future research prospects are the role of Ga-68 Dotatate in treatment and in follow-up imaging of MPNSTs in NF1 patients.

Gallium-68 DOTATATE for Detecting Malignant Peripheral Nerve Sheath Tumors in NF1-Associated Plexiform Neurofibromas

Revealing Hidden Pathogens: Culture-Negative Vertebral Osteomyelitis Diagnosed via Plasma DNA Sequencing

Trishtha Agarwal, MD1; David Kornblum, MD2; Kartikeya Cherabuddi, MD2; Jacqueline Sherbuk, MD2
1Department of Internal Medicine, Kasturba Medical College, Manipal, Karnataka , India
2Department of Infectious Disease, University of South Florida, Tampa, FL, USA



Background - Vertebral osteomyelitis (VO) is a rare but potentially debilitating infection, commonly resulting from hematogenous spread. While typical pathogens include Staphylococcus aureus and gram-negative bacilli, rare organisms such as Candida albicans and Aerococcus urinae have emerged in specific patient populations, particularly those with recent urologic procedures. The valveless vertebral venous plexus (Batson’s plexus) facilitates retrograde spread from the pelvic organs to the spine, even in the absence of systemic bacteremia. Diagnosis is often delayed due to nonspecific symptoms and low culture yield.

Case Presentation - A 66-year-old male with a history of ureteral stent placement presented with seven weeks of progressive lower back pain and unintentional weight loss. MRI revealed L4-L5 vertebral osteomyelitis with epidural phlegmon and psoas myositis. Blood cultures and CT-guided biopsy were negative. Plasma microbial cell-free DNA sequencing (Karius test) identified Candida albicans and Aerococcus urinae. Given the patient’s recent genitourinary instrumentation, these organisms were considered causative. He was treated with intravenous ceftriaxone and oral fluconazole and discharged with a peripherally inserted central catheter (PICC) line for outpatient therapy.

Discussion- This is the first documented case of vertebral osteomyelitis due to concurrent C. albicans and A. urinae, likely seeded hematogenously from the urinary tract via Batson’s plexus. It underscores the value of cell-free DNA sequencing in diagnosing culture-negative spinal infections and supports its early use in patients with compatible clinical and radiologic features when conventional testing is nondiagnostic.










Revealing Hidden Pathogens: Culture-Negative Vertebral Osteomyelitis Diagnosed via Plasma DNA Sequencing


Background
Sickle cell disease (SCD) is a hereditary hemoglobinopathy affecting ~100,000 individuals in the United States. While SCD increases the risk of hematologic malignancies, large cohort studies report the incidence of solid tumors—including breast cancer—remains below 2%, lower than in age-matched controls. This rarity likely reflects the chronic hypoxic, antiangiogenic, and inflammatory environment in SCD, which may suppress tumor angiogenesis and growth. As management improves and survival increases, age-related cancers are rising. This vignette illustrates diagnostic and management challenges of breast cancer in SCD and highlights emerging evidence on this rare co-occurrence.

Case Presentation
A 58-year-old African American woman with homozygous SCD, hypertension, and
proteinuria, compliant with routine screenings, underwent annual mammography. In 2022, grouped microcalcifications were detected in the left breast, but an initial biopsy was inconclusive. Repeat imaging and biopsy in 2024 revealed a 0.5 cm, moderately to poorly differentiated invasive ductal carcinoma (IDC) with high-grade ductal carcinoma in situ (DCIS) and microcalcifications. The tumor was hormone receptor-positive and HER2- negative. She underwent lumpectomy and re-excision; sentinel lymph nodes were negative. Oncotype DX testing showed a Recurrence Score of 38(0-100), calculated from RT-PCR analysis of 21 genes, corresponding to a 9-year distant recurrence risk of 26% (95% CI: 20%–34%) and chemotherapy benefit exceeding 15% (95% CI: 9%–37%). Due to concern about complications, she declined chemotherapy and received radiotherapy and anastrozole. She is eligible for Ribociclib plus endocrine therapy under NATALEE trial criteria, supporting its use as a new adjuvant option.

Discussion
Recent population-based studies provide insights into cancer risk in SCD. A 23-year
California registry analysis found SCD patients had a 38% lower risk of solid tumors,
including breast cancer, despite a 72% higher risk of hematologic malignancies. Similar findings emerged from North Carolina, where only 1.9% of SCD patients developed solid tumors, with breast cancer a small minority. Mechanistic studies suggest chronic hypoxia in SCD upregulates hypoxia-inducible factors
and alters immune function, potentially suppressing angiogenesis and modulating immune surveillance. Experimental data indicate the SCD microenvironment impairs
neovascularization and may limit solid tumor growth and spread. However, as management advances and lifespan increases, cumulative risk of age-related malignancies, including breast cancer, is expected to rise.
This case highlights individualized screening and treatment in SCD, balancing benefit with the risk of complications. It emphasizes the need for continued epidemiological surveillance and mechanistic research to clarify risk and guide treatment in this population.

Invasive Breast Carcinoma in a Patient with Sickle Cell Anemia: A
Rare Clinical Intersection

Mirchandani S¹, Paryani R¹, Bhawnani N², Ray I³, Kantheti H⁴
¹ UConn Health, ² Bharati Vidyapeeth Medical College, Pune, India, ³ MGM Medical College, Indore, India, ⁴ Baylor Scott & White Saints Medical Center
Background
Dizziness has a broad differential diagnosis. The coexistence of Mobitz atrioventricular (AV)
block, postural orthostatic tachycardia syndrome (POTS), and superior canal dehiscence
syndrome (SCDS) creates a significant diagnostic challenge, especially with symptom overlap
from endocrine conditions like adrenal insufficiency. A systematic evaluation is crucial, as SCDS
remains an underrecognized diagnosis.

Case Presentation
We present the case of a 23-year-old woman (G2P1) whose complex postpartum course was
marked by overlapping cardiovascular, vestibular, and autoimmune features. Initially admitted at
31 weeks gestation in June 2024 with headache and right upper quadrant pain, she developed
preeclampsia with severe features and HELLP syndrome, requiring an emergent Cesarean
section. Postpartum, she had severe hypertension requiring multi-agent therapy and persistent
leukocytosis and tachycardia consistent with SIRS of unclear etiology.
Six weeks later, she was readmitted with new-onset right upper extremity weakness, chest pain,
and cognitive symptoms along with lower extremity swelling. Workup revealed proteinuria,
elevated ESR, and high C3 complement, with negative ANA and unremarkable ECHO and MRI
aside from a small thoracic syrinx. Given her family history of lupus and stroke, she was referred
to Rheumatology and Psychology.
Outpatient Holter monitoring showed frequent supraventricular tachycardia and asymptomatic
second-degree Mobitz Type I AV block. Her antihypertensive regimen was switched from
labetalol to losartan. In September 2024, she was rehospitalized with exertional tachycardia up
to 170 bpm and orthostatic symptoms. Formal vitals showed a >30 bpm rise on standing without
hypotension, consistent with POTS. Ivabradine was initiated with favorable effect.
Despite treatment, she continued to experience debilitating dizziness, tinnitus, and imbalance
and complained of autophony. In March 2025, high-resolution temporal bone CT and MRI
identified bilateral superior semicircular canal dehiscence (SCDS), explaining her vestibular
symptoms. She was referred to ENT for possible surgical repair. Given persistent fatigue and
hypotension, endocrine workup revealed low-normal ACTH and indeterminate morning cortisol,
prompting referral for dynamic adrenal testing.This case highlights the diagnostic challenge of postpartum multisystem disorders and the
importance of a multidisciplinary approach when cardiovascular, vestibular, endocrine, and
autoimmune features coexist.

Discussion
In patients presenting with multifaceted dizziness, particularly with a complex medical history, it
is crucial to consider concurrent cardiac, autonomic, and vestibular disorders. This case
underscores the importance of thorough investigation, including Holter monitoring and
orthostatic testing, to identify distinct but coexisting conditions like AV block and POTS. Heart
Rhythm Society's 2015 Expert Consensus Statement also mentions ivabradine as a promising
treatment for POTS, noting that approximately 60% of patients experienced symptom
improvement in an open-label study.



Vertigo, Vital Signs, and Hormones: A Triple Threat of SCDS, POTS with Heart block and Addison's

Ependymomas are rare tumors that arise from ependymal cells lining the brain and spinal cord, accounting for 1.2% to 7.8% of intracranial tumors and 2% to 6% of gliomas. In children, they are the most common primary brain tumors after pilocytic astrocytomas and medulloblastomas. Elevated intracranial pressure (ICP) is common in children with CNS tumors and can result from the tumor's mass effect or obstructive hydrocephalus.
Current Paradigm: Managing acute hydrocephalus typically involves cerebrospinal fluid (CSF) diversion methods such as endoscopic third ventriculostomy (ETV), external ventricular drainage (EVD), or ventriculoperitoneal (VP) shunt.
Challenges: EVDs carry risks like infection and dysfunction. VP shunts can lead to mechanical failures and infections, often requiring further surgery. ETV, while generally safe, can have complications like hemorrhage, damage to brain structures, CSF leaks, and rare instances of sudden death. 
Novelty of Case: This case demonstrates a successful alternative: immediate tumor resection in a critically ill toddler without prior CSF diversion, challenging the conventional approach.

Resection First: Avoiding Preoperative Shunting in a Critically Ill Toddler with Posterior Fossa Ependymoma and Acute Hydrocephalus

Migraine is a prevalent neurological disorder characterized by unilateral, pulsating headaches that may be accompanied by photophobia, phonophobia, and nausea. It is broadly categorized into migraine with aura and without aura, with the former presenting transient neurological disturbances, most notably visual phenomena that can mimic stroke. This diagnosticoverlap is compounded by limitations in conventional stroke assessment tools, which often underrepresent visual field deficits. Emerging evidence suggests that migraine, particularly with frequent auras, is associated with an elevated risk of stroke. Though there is good evidence to support the association of migraine with aura and ischemic stroke, there is limited understanding of the pathophysiology and underlying causation. 
A case study of a 68-year-old male with a history of acephalgic ocular migraines exemplifies these challenges. This patient presented to the emergency department (ED) with a chief complaint of headache and visual changes, specifically right-sided scintillating scotoma, for a period of 9 hours. Notably, the patient did not have a history of headache with his migraines, and the visual phenomenon would terminate approximately 6–8 hours on its own, without any residual deficit. Non-contrast CT of the head showed no abnormality. Joint decision-making by the patient and provider concluded that these symptoms were highly suggestive of migraine, and no further workup was done, even with SNOOP criteria being met. Two days later, the patient presented to the ED again with a chief complaint of the right-sided scintillating scotoma transforming into right-sided inferior quadrantanopia. MRI revealed acute infarction of the left occipital lobe. The remaining laboratory studies, CT angiogram of the head and neck, echocardiogram, and telemetry were unremarkable. Upon neurology outpatient follow-up, with a history of acephalgic migraines in the same cerebral territory, with no evidence of thrombotic or embolic activity, migrainous stroke was diagnosed. 
There is a well-established association between migraine with aura and increased risk of stroke. However, migrainous stroke remains a diagnosis of exclusion due to lack of definitive causation. This synthesis highlights the association between the two disease processes and suggests probable pathophysiology regarding neurogenic inflammation, vascular risk factors, and hypercoagulable states (e.g., endothelin-1 and von Willebrand factor). Furthermore, it emphasizes the significance of a thorough workup including non-contrast CT, MRI, and laboratory testing to differentiate migrainous events from strokes, particularly important when SNOOP criteria are met. Further research is needed to continue to assess the pathophysiology of stroke in patients with migraine with aura.

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