====== Idiopathic normal pressure hydrocephalus pathophysiology ====== The full clinical triad is not prevalent in all of the cases and the [[pathophysiology]] of iNPH remains unclear. For many years, the [[pathophysiology]] of idiopathic [[intracranial hypertension]] (IIH) was interpreted as "secondary intracranial hypertension," and IIH was considered to be caused by [[brain edema]] due to [[obstructive sleep apnea]]. Another theory proposed cerebrospinal fluid (CSF) absorption impairment due to excessive medication with [[vitamin A]] derivatives. Other reports pointed out the importance of [[obesity]], which may cause an impairment of intracranial venous drainage due to elevated right atrial pressure ((Miyachi S, Hiramatsu R, Ohnishi H, Takahashi K, Kuroiwa T. Endovascular Treatment of Idiopathic Intracranial Hypertension with Stenting of the Transverse Sinus Stenosis. Neurointervention. 2018 Sep;13(2):138-143. doi: 10.5469/neuroint.2018.00990. Epub 2018 Oct 1. PubMed PMID: 30196687; PubMed Central PMCID: PMC6132029. )). ---- Kamalian et al. conducted an in-depth [[proteomics]] of [[cerebrospinal fluid]] (CSF) in 28 shunt-responsive [[idiopathic normal pressure hydrocephalus]] patients, 38 Mild [[Cognitive Impairment]] (MCI) due to [[Alzheimer's disease]], and 49 healthy controls. Utilizing the Olink Explore 3072 panel, they identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside [[vimentin]] and inflammatory markers upregulation, these results suggest [[ependyma]]l layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with [[congenital hydrocephalus]] (e.g., [[L1CAM]], [[PCDH9]], [[ISLR2]], [[ADAMTSL2]], and [[B4GAT1]]) points to a possible shared molecular foundation between [[congenital hydrocephalus]] and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the [[idiopathic normal pressure hydrocephalus pathophysiology]], with implications for improved [[idiopathic normal pressure hydrocephalus diagnosis]] ((Kamalian A, Shirzadeh Barough S, Ho SG, Albert M, Luciano MG, Yasar S, Moghekar A. Molecular [[signature]]s of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid. Fluids Barriers CNS. 2024 Aug 8;21(1):64. doi: 10.1186/s12987-024-00561-5. PMID: 39118132.)). ---- Disturbed cerebrospinal fluid (CSF) dynamics are part of the pathophysiology of normal pressure hydrocephalus (NPH). A study investigated the contribution of established CSF dynamic parameters to mean [[pulse amplitude]] (AMP), a prognostic variable defined as mean amplitude of cardiac-related intracranial pressure pulsations during 10 min of [[lumbar infusion test]], with the aim of clarifying the physiological interpretation of the variable. AMP(mean) and CSF dynamic parameters were determined from infusion tests performed on 18 patients with suspected NPH. Using a mathematical model of CSF dynamics, an expression for AMP(mean) was derived and the influence of the different parameters was assessed. There was high correlation between modelled and measured AMP(mean) (r = 0.98, p < 0.01). Outflow resistance and three parameters relating to compliance were identified from the model. Correlation analysis of patient data confirmed the effect of the parameters on AMP(mean) (Spearman's ρ = 0.58-0.88, p < 0.05). Simulated variations of ±1 standard deviation (SD) of the parameters resulted in AMP(mean) changes of 0.6-2.9 SD, with the elastance coefficient showing the strongest influence. Parameters relating to compliance showed the largest contribution to AMP(mean), which supports the importance of the compliance aspect of CSF dynamics for the understanding of the pathophysiology of NPH ((Qvarlander S, Malm J, Eklund A. CSF dynamic analysis of a predictive pulsatility-based infusion test for normal pressure hydrocephalus. Med Biol Eng Comput. 2014 Jan;52(1):75-85. doi: 10.1007/s11517-013-1110-1. Epub 2013 Oct 23. PubMed PMID: 24151060. )).