Targeting Sleep and the Glymphatic Pathway to Improve Stroke Rehabilitation Outcomes: Joyce Lee-Iannotti, MD, FAAN, FAASM

WATCH TIME: 5 minutes

"If we can institute something like DORAs and rev up the glymphatic system, maybe stroke patients will have better outcomes and recovery. Sleep should be at the top of the list, just like diabetes, high cholesterol, and hypertension."

The glymphatic system–a brain-wide perivascular network responsible for clearing interstitial waste–is increasingly recognized as playing a key role in stroke pathophysiology and recovery. Growing research has shown that ischemic and hemorrhagic strokes both impair glymphatic flow, which may occur because of cerebral edema and increased intracranial pressure, disruption of aquaporin-4 polarization, or blood-brain barrier breakdown.

At the 2025 SLEEP Annual Meeting, held June 8-11 in Seattle, Washington, NeurologyLive^® sat down with sleep and stroke expert Joyce Lee-Iannotti, MD, FAAN, FAASM, to discuss her presentation on the glymphatic system and how it pertains to stroke. Lee-Iannotti, a neurologist at Barrow Neurological Institute, has a number of years of experience with the diagnosis and treatment of neurovascular diseases and sleep disorders, with a particular specialty in central disorders of hypersomnia, REM sleep behavior disorder, and sleep-wake disturbances in long COVID.

In the interview, Lee-Iannotti was asked about targeted ways to impact the glymphatic system to potentially lowed the odds of recurrent stroke and additional complications. She spoke on how the glymphatic system’s function in clearing neurotoxic waste could be leveraged to improve stroke outcomes, especially through sleep-focused strategies. She emphasized emerging pharmacologic approaches—such as dual orexin receptor antagonists (DORAs) and omega-3 fatty acids—that may enhance glymphatic activity and improve neurologic recovery post-stroke. Lee-Iannotti, who also serves as division chief at the Petznick Stroke Center at Barrow, discussed the need for broader clinician awareness about the role of sleep in neurologic disease and advocated for updating post-stroke care checklists to prioritize sleep quality as a key determinant of recovery.

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