Implications of the glymphatic system in the pathogenesis of normal pressure hydrocephalus: an illustrated scoping review

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the clinical triad of cognitive impairment, gait disturbances, and urinary incontinence, coupled with ventricular enlargement on brain imaging. The pathophysiology of iNPH remains complex, with varied patient responses to CSF diversion and a generally progressive nature of the disease. This scoping review aimed to provide an overview of the glymphatic system (GS) and its role in the development of iNPH. The review highlights the crucial function of the GS in maintaining brain homeostasis by clearing waste products from the interstitial space. Dysfunction in this system leads to impaired CSF clearance, resulting in the accumulation of neurotoxic substances that contribute to the symptoms of iNPH. Additionally, potential shared pathophysiological pathways between iNPH and other conditions affecting the GS such as aging, diabetes mellitus, hypertension, and sleep disorders are discussed. The findings suggest that GS dysfunction is a key factor in iNPH pathogenesis and may also be linked to the disease's poor responsiveness to shunt treatment. By enhancing understanding of these mechanisms, there is potential to develop targeted therapies aimed at restoring glymphatic function, thereby improving outcomes for patients with iNPH.