Freddi Segal-Gidan is Director of the Rancho Los Amigos/University of Southern California (USC) Alzheimer’s Disease Center and Assistant Clinical Professor in the departments of Neurology and Family Medicine at Keck School of Medicine, USC, and in Gerontology at L. Davis School of Gerontology at USC, Los Angeles.
PATHOPHYSIOLOGY The underlying pathophysiology of iNPH is not completely understood. The symptoms are believed to arise from the slow, gradual, and insidious accumulation of CSF within the brain ventricles. The current understanding is that the CSF acts as a lymphatic drainage system for the brain, entering the brain parenchyma via paravascular spaces that surround penetrating arteries and clearing interstitial fluid along paravenous drainage pathways.4
CSF reabsorption into the blood is a dual process, with drainage via the arachnoid villi and granulations within the dural sinuses and slow drainage via lymphatic vessels in the perineural, otic, and ophthalmic regions. There is a pressure gradient of fluid in the subarachnoid space and ventricles, with the CSF pressure normally higher than the pressure of the venous system, allowing outflow of CSF.
In iNPH, outflow of CSF is at least partially disrupted, and there is decreased CSF reabsorption, resulting in a higher, normal baseline CSF volume over time. The underlying cause of reduced CSF reabsorption in iNPH remains uncertain, but it has been proposed that arachnoid granulations fail to maintain adequate removal of CSF, possibly due to fibrosis or scarring.5 In response to increased CSF volume, the ventricles distend and compress the brain parenchyma. Exactly how the pressure exerted by the ventricles leads to changes in gait, cognition, and urinary incontinence is not well understood.
