Accumulation of Macromolecules in Idiopathic Normal Pressure Hydrocephalus

Akiyama, Yukinori; Yokoyama, Rintaro; Takashima, Hiroyuki; Kawata, Yuka; Arihara, Masayasu; Chiba, Ryohei; Kimura, Yusuke; Mikami, Takeshi; Mikuni, Nobuhiro

doi:10.2176/nmc.oa.2020-0274

Cited by 10 publications

(5 citation statements)

References 17 publications

(23 reference statements)

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“…The reasons explaining the unchanged protein concentrations in NPH and communicating HC patients are unclear, but other abnormalities, and even possible treatment, have been described [ 24 , 25 ]. Impaired counterregulatory reduction might even be a pathophysiological momentum in the genesis of those chronic hydrocephalic states [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Protein Concentrations in Hydrocephalus

et al. 2023

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CSF protein levels are altered in neurological disorders, such as hydrocephalus of different etiologies. In this retrospective observational study, we analyzed cerebrospinal fluid (CSF) samples in hydrocephalic diseases such as aqueductal stenosis (AQS, n = 27), normal pressure hydrocephalus (NPH, n = 24), hydrocephalus communicans (commHC, n = 25) and idiopathic intracranial hypertension (IIH)/pseudotumor cerebri (PC, n = 7) in comparison with neurological patients without hydrocephalic configuration (control, n = 95). CSF was obtained through CSF diversion procedures and lumbar punction and analyzed for protein concentrations according to the institution’s laboratory standards. We found significantly decreased CSF protein levels in patients suffering from AQS (0.13 mg/dL [0.1–0.16 mg/dL] p = 2.28 × 10−8) and from PC (0.18 mg/dL [0.12–0.24 mg/dL] p = 0.01) compared with controls (0.34 mg/dL [0.33–0.35 mg/dL]). Protein levels were not altered in patients suffering from commHC and NPH compared with neurologically healthy individuals. We propose that a decrease in CSF protein levels is part of an active counterregulatory mechanism to lower CSF volume and, subsequently, intracranial pressure in specific diseases. Research regarding said mechanism and more specific proteomic research on a cellular level must still be performed to prove this hypothesis. Differences in protein levels between different diseases point to different etiologies and mechanisms in different hydrocephalic pathologies.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Protein Concentrations in Hydrocephalus

et al. 2023

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“…It is known that pulsatility in the CSF space is increased in iNPH patients [ 15 , 42 ]. Investigations of the glympathic system in iNPH patients using DTI and MR spectroscopy showed altered function of the glymphatic system, in part shown by an accumulation of macromolecules and a decreased leven of N-acetyl aspartate [ 43 – 45 ]. Our current findings of early presence of WMH can support the abnormal findings of the glympathic system in iNPH patients and seem to point into this direction for the etiology of iNPH.…”

Section: Discussionmentioning

confidence: 99%

Incidental findings of typical iNPH imaging signs in asymptomatic subjects with subclinical cognitive decline

Engel

Pirpamer

Hofer

et al. 2021

Fluids Barriers CNS

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Background The etiology of idiopathic normal pressure hydrocephalus (iNPH) remains unclear. Little is known about the pre-symptomatic stage. This study aimed to investigate the association of neuropsychological data with iNPH-characteristic imaging changes compared to normal imaging and unspecific atrophy in a healthy population. Methods We extracted data from the community-dwelling Austrian Stroke Prevention Family Study (ASPS-Fam) database (2006–2010). All subjects underwent a baseline and identical follow-up examination after 3–5 years with MR imaging and an extensive neuropsychological test battery (Trail Making Test B, short physical performance balance, walking speed, memory, visuo-practical skills, composite scores of executive function and g-factor). We categorized the subjects into “iNPH”-associated, non-specific “atrophy,” and “normal” based on the rating of different radiological cerebrospinal fluid (CSF) space parameters. We noted how the categories developed over time. We assessed the association of the image categories with the neuropsychological data, different demographic, and lifestyle parameters (age, sex, education, alcohol intake, arterial hypertension, hypercholesterolemia), and the extent of white matter hyperintensities. We investigated whether neuropsychological data associated with the image categories were independent from other parameters as confounders. Results One hundred and thirteen subjects, aged 50–70 years, were examined. The imaging category “iNPH” was only present at follow-up. A third of subjects with “atrophy” at baseline changed to the category “iNPH” at follow-up. More white matter hyperintensities (WMH) were present in later “iNPH” subjects. Subjects with “iNPH” performed worse than “normal” subjects on executive function (p = 0.0118), memory (p = 0.0109), and Trail Making Test B (TMT-B. p < 0.0001). Education, alcohol intake, diabetes, arterial hypertension, and hypercholesterolemia had no effect. Age, number of females, and the extent of white matter hyperintensities were higher in “iNPH” than in “normal” subjects but did not significantly confound the neuropsychological results. Conclusions Apparent asymptomatic subjects with “iNPH” imaging characteristics presented with subclinical cognitive decline and showed worse executive function, memory, and TMT-B results than “normal” subjects. WMH seem to play a role in the etiology before ventriculomegaly. Clinical screening of individuals with incidental iNPH-characteristic imaging and conspicuous results sof these neurocognitive tests needs further validation.

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“…The other nine metabolites, such as glyceric acid, were not significantly different between the two groups in the validation cohort. It should be noted that all three differential metabolites have been reported to change significantly in patients with NPH 18,54,55 and are correlated with Evans' ratio, which measures NPH‐induced ventricular enlargement. These results indicate the reliability of our metabolomic study.…”

Section: Discussionmentioning

confidence: 99%

Increasing brain N‐acetylneuraminic acid alleviates hydrocephalus‐induced neurological deficits

Wang,

Nie,

Gao

et al. 2023

CNS Neurosci Ther

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AimsThis metabolomic study aimed to evaluate the role of N‐acetylneuraminic acid (Neu5Ac) in the neurological deficits of normal pressure hydrocephalus (NPH) and its potential therapeutic effect.MethodsWe analyzed the metabolic profiles of NPH using cerebrospinal fluid with multivariate and univariate statistical analyses in a set of 42 NPH patients and 38 controls. We further correlated the levels of differential metabolites with severity‐related clinical parameters, including the normal pressure hydrocephalus grading scale (NPHGS). We then established kaolin‐induced hydrocephalus in mice and treated them using N‐acetylmannosamine (ManNAc), a precursor of Neu5Ac. We examined brain Neu5Ac, astrocyte polarization, demyelination, and neurobehavioral outcomes to explore its therapeutic effect.ResultsThree metabolites were significantly altered in NPH patients. Only decreased Neu5Ac levels were correlated with NPHGS scores. Decreased brain Neu5Ac levels have been observed in hydrocephalic mice. Increasing brain Neu5Ac by ManNAc suppressed the activation of astrocytes and promoted their transition from A1 to A2 polarization. ManNAc also attenuated the periventricular white matter demyelination and improved neurobehavioral outcomes in hydrocephalic mice.ConclusionIncreasing brain Neu5Ac improved the neurological outcomes associated with the regulation of astrocyte polarization and the suppression of demyelination in hydrocephalic mice, which may be a potential therapeutic strategy for NPH.

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Accumulation of Macromolecules in Idiopathic Normal Pressure Hydrocephalus

Cited by 10 publications

References 17 publications

Cerebrospinal Fluid Protein Concentrations in Hydrocephalus

Cerebrospinal Fluid Protein Concentrations in Hydrocephalus

Incidental findings of typical iNPH imaging signs in asymptomatic subjects with subclinical cognitive decline

Increasing brain N‐acetylneuraminic acid alleviates hydrocephalus‐induced neurological deficits

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