Neurology® Podcast Monogenic Mimics of Neuroinflammatory Phenotypes in Children and Young Adults - Part 2
Jan 12, 2026
Dr. Ayush Gupta, a neurologist and researcher in neurological sciences, dives into the intriguing world of monogenic disorders mimicking neuroinflammatory conditions. He highlights essential clinical clues for diagnosing LBSL and late-onset Alexander disease. The discussion also covers the importance of genetic testing, addressing the challenges of interpreting variants of uncertain significance, and the necessity of collaboration with genetic counselors. Gupta emphasizes recognizing key red flags in nonresponsive cases, urging clinicians to refine their diagnostic approaches.
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Spinal Imaging Clues Point To Genetic Causes
- Leukoencephalopathies can mimic longitudinally extensive myelopathy when they target dorsal columns and corticospinal tracts.
- Symmetry, progressive course, and lactate elevation point toward LBSL rather than acute inflammatory myelitis.
Age Alters Genetic Disease Presentations
- Age-dependent phenotypes can make classic pediatric leukodystrophies appear milder or different in adults.
- Late-onset presentations (e.g., Alexander disease) may show medullary and spinal atrophy with a tadpole-like MRI sign.
Don’t Overinterpret VUS Without Correlation
- When you find variants of uncertain significance, pause and consult neurogenetics for functional correlation before declaring a genetic diagnosis.
- Seek functional studies or family segregation to confirm pathogenicity rather than over-interpreting uncertain variants.