Abstract Details

Title Recurrent Cerebral Ischemic Events in a Patient with a POLG Gene Mutation: A Case Report

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 14-015

Objective

Report a case of stroke-like events in a young patient with a mutation in the POLG gene, highlighting the differential diagnosis for recurrent cerebral ischemia.

Background Ischemic stroke is one of the leading causes of death globally. Major risk factors include hypertension, diabetes, and smoking, though genetic alterations play a role in some cases.

Design/Methods Not applicable.

Results Female patient, smoker, hypertense, and with a maternal familiar history of cerebrovascular disease. At 58 experienced her first vascular event. Diagnosed with hypertensive stroke, residual hemiparesis, and dysarthria as sequelae. A year later, she was rehospitalized due to worsening dysarthria. A CT scan revealed ischemic sequelae and severe microangiopathy, confirmed by MRI, which showed a recent ischemic event and Fazekas grade 3 microangiopathy. She was discharged with a presumptive CADASIL diagnosis. Her condition worsened over the following months, with functional decline, and behavioral changes. By age 61, she was fully dependent for daily activities and was rehospitalized for seizures and global aphasia. New ischemic lesions were found on imaging. Genetic testing ruled out NOTCH3 mutations but revealed a heterozygous variant of uncertain significance (VUS) in the DNA polymerase gamma (POLG) gene (c.752C>T, p.Thr251Ile), linked to mitochondrial function. The final diagnosis was a POLG-related disorder with stroke-like episodes. Due to the extensive ischemic damage and complete loss of function, palliative care was recommended.

Conclusions

POLG is a human mitochondrial DNA polymerase, essential for maintaining DNA integrity. Mutations in the POLG gene are linked to syndromes such as Alpers-Huttenlocher syndrome; however, ischemic stroke is a rare manifestation. Similar to stroke-like episodes observed in MELAS (mitochondrial encephalopathy associated with lactic acidosis and stroke-like lesions), the pathophysiology may involve endothelial dysfunction. A definitive diagnosis requires genetic testing. Management is supportive, as demonstrated in this case. This report underscores the importance of considering genetic mutations in patients with recurrent ischemic events.

Authors/Disclosures
TAIS L. DENICOL, MD PRESENTER	Miss DENICOL has nothing to disclose.
Juan S. Sánchez León, Sr., MD	Dr. Sánchez León has nothing to disclose.
Carolina Matté Dagostini	Miss Matté Dagostini has nothing to disclose.
Renato Dumbá D. de Castro, Sr., MD	Mr. de Castro has nothing to disclose.
Fernanda Broch, MD	Miss Cínica has nothing to disclose.
Pedro H. Ruschel, MD	Mrs. Ruschel has nothing to disclose.
KARLA S. SANDOVAL CASTRO, MD	Dr. SANDOVAL CASTRO has nothing to disclose.

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