Sleep-Disordered Breathing and Idiopathic Normal-Pressure Hydrocephalus: Recent Pathophysiological Advances

Abstract

Purpose of Review Idiopathic normal-pressure hydrocephalus (iNPH) is characterized clinically by ventriculomegaly, abnormal gait, falls, incontinence, and cognitive decline. This article reviews recent advances in the pathophysiology of iNPH concerning sleep-disordered breathing (SDB) and glymphatic circulation during deep sleep. Recent Findings The authors found iNPH frequently associated with obstructive sleep apnea (OSA). A critical factor in iNPH is intracranial venous hypertension delaying drainage of cerebrospinal fluid (CSF) into the cerebral venous sinuses. CSF-venous blood circulates in the jugular veins and finally drains into the heart. During SDB, repeated reflex attempts to breathe induce strong respiratory efforts against a closed glottis thereby increasing the negative intrathoracic pressure. This causes atrial distortion and decreases venous return to the heart resulting in retrograde intracranial venous hypertension. Additionally, repeated awakenings from OSA impede sleep-associated circulation of interstitial CSF into the glymphatic circulation contributing to hydrocephalus. Summary Sleep has become a critical element in the cognitive changes of aging including iNPH.

Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus

“…Thirdly, sleep disorders are frequently diagnosed among iNPH patients. A study among 31 iNPH subjects revealed that all iNPH patients suffered from sleep abnormality to different extent 95 . Over 90.3% of iNPH patients had an obstructive sleep apnea 95 .…”

“…A study among 31 iNPH subjects revealed that all iNPH patients suffered from sleep abnormality to different extent 95 . Over 90.3% of iNPH patients had an obstructive sleep apnea 95 . Sleep abnormality could promote the overnight accumulation of metabolites in the interstitial space.…”

“…Sleep abnormality could promote the overnight accumulation of metabolites in the interstitial space. It is hypothesized that repeated inspiratory movements against tongue‐blocked airway lead to elevated intrathoracic negative pressure and reduced venous return, which ultimately cause intracranial venous hypertension and iNPH 95 …”

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

“…Our results don't back up this finding, but it must be noted that our questionnaire represents only the time close to the diagnosis and not their alcohol consumption earlier in life. Also, a frequent association between iNPH and obstructive sleep apnea has been found [45]. Our analysis with the probable fNPH families showed no differences in the prevalence of sleep apnea between the groups (Table 3).…”

“…There is evidence that the glymphatic system dysfunction could affect the development of iNPH [ 41 – 43 ]. It has been suggested that in iNPH the glymphatic system is possibly impaired through neuroinflammation, reactive astrogliosis, depolarization and reduced density of aquaporin-4 (AQP4) and sleep disturbances, which could reduce the normal clearance of CSF [ 43 – 45 ]. Interestingly in rat models, diabetes has been found to cause glymphatic system dysfunction, reduction in AQP4 density, neuroinflammation, microvascular damage, blood–brain barrier damage and cognitive decline that could be associated with glymphatic system dysfunction [ 46 – 49 ].…”