2026 American Academy of Neurology Abstract Website

Sonal Sharma¹, Albert Wu², Sara Nguyen³, Reza Abdavies⁴, Zarazuela Zolkipli-Cunningham⁵, Muhammad Saleh⁶
¹Children's Hospital of Philadelphia, Division of Neurology; Perelman School of Medicine, University of Pennsylvania, ²Perelman School of Medicine, University of Pennsylvania, ³Children's Hospital of Philadelphia, Division of Genetics, ⁴Children's hospital of Philadelphia, Department of Radiology, ⁵The Children's Hospital of Philadelphia, Division of Genetics; Perelman School of Medicine, University of Pennsylvania, ⁶Children's hospital of Philadelphia, Department of Radiology; Perelman School of Medicine, University of Pennsylvania

Objective:

Novel evaluation of brain glutathione (GSH) levels in Primary Mitochondrial Disease (PMD) patients by edited Magnetic Resonance Spectroscopy (MRS) compared to healthy controls.

Background:

PMD are genetic disorders presenting with neurodegeneration and metabolic strokes, linked to cellular redox imbalance and altered antioxidant status evidenced by blood GSH levels. Measurement of GSH levels in brain has never been performed.

Design/Methods:

Nine PMD patients and seven healthy controls were studied. Clinical data and GSH levels were measured in specific brain regions [Anterior Cingulate Cortex (ACC), left motor cortex, bilateral thalamus, cerebellum]. Regional GSH levels were compared using the Mann–Whitney U test.

Results:

Among 9 genetically confirmed patients (4/9 males; ages 9-35) with PMD, genetic etiologies included MT-TL1 (n=6), NUBPL, MT-TV, and MT-ND4 (n=1 each). Five patients were on N-acetylcysteine (NAC, a precursor of GSH). GSH levels for the NAC-treated patients (group 1) were 3.21-4.62 in ACC, 2.82-5.13 in motor cortex, 5.09-10.14 in thalamus, and 2.72-7.91 IU in cerebellum. Meanwhile, untreated patients (group 2, n=4) had GSH levels of 3.09-4.35 in ACC, 2.58-3.50 in motor cortex, 3.37-6.13 in thalamus, and 4.50-6.21 IU in cerebellum. In 7 controls (5/7 males; ages 11-41), GSH was 3.25-4.73 in ACC, 2.16-3.39 in motor cortex, 2.43-5.88 in thalamus, and 3.25-6.15 IU in cerebellum. NAC-treated group 1 patients showed no significant mean GSH difference from controls in ACC (p=0.68) or thalamus (p=0.56) but higher in motor cortex (p=0.042) and significantly in cerebellum (p=0.004). Untreated group 2 revealed no significant differences in ACC (p=0.57), motor cortex (p=0.44), or thalamus (p=0.44), significantly higher in cerebellum (p=0.008).

Conclusions:

Preliminary results reveal that cerebellar GSH levels were higher in the NAC-treated and untreated PMD patients as compared to controls. GSH levels in the motor cortex were specifically elevated in treated patients. Active studies in a larger cohort are ongoing.