Neurosteroids as potential markers for the diagnosis of normal pressure hydrocephalus — ASN Events
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  2. Poster Session 1 - Hormones and higher brain function
  3. Neurosteroids as potential markers for the diagnosis of normal pressure hydrocephalus

Neurosteroids as potential markers for the diagnosis of normal pressure hydrocephalus (#205)

Lucie Sosvorova 1 , Jana Kubatova 1 , Martin Hill 1 , Marie Bicikova 1 , Milan Mohapl 2 , Richard Hampl 1
  1. Department of Steroids and Proteofactors, Institute of Endocrinology, Prague, Czech Republic
  2. Department of Neurosurgery, Central Military Hospital, Prague, Czech Republic

Background: Normal pressure hydrocephalus (NPH) is treatable neurological disorder manifested as the triad of balance impairment, urinary incontinence and dementia development caused by disorders in the cerebrospinal fluid (CSF) reabsorption. It develops mainly in elderly people, where the prevalence ranged from 0.2% to 5.9% increasing with the age.1 NPH symptoms are potentially reversible, when early recognized. Diagnosis is difficult and can be easily mistaken for other neurodegenerative diseases. This makes NPH one of worldwide misdiagnosed problems.

Dehydroepiandrosterone (DHEA) and its oxo-/hydroxy- metabolites occurring in the brain are considered neurosteroids. Their metabolism employs the activity of 11β-hydroxysteroid dehydrogenase which also carries out the oxidation/reduction of cortisol and cortisone.2 Cortisol and aldosterone compete for mineralocorticoid receptors in the brain and may influence osmotic gradient. The levels of homocysteine, an independent risk factor for dementia development, are also of interest.

Aim of the study was to find out CSF and plasma markers that would simplify the NPH diagnosis.

Methods: In our patients (n=35; NPH, 65-80 years) and controls (n=35; excluded NPH, 65-80 years), the levels of CSF and plasma cortisol, cortisone, 7α-OH-DHEA, 7β-OH-DHEA, 7-oxo-DHEA, 16α-OH-DHEA, aldosterone, DHEA (all LC-MS/MS) DHEAs (RIA) and homocysteine (GC-FID) were determined.

Results: The plasma levels of 7α-OH-DHEA, 7β-OH-DHEA, 7-oxo-DHEA, DHEA and DHEAs and the CSF levels of 7β-OH-DHEA, 7-oxo-DHEA, DHEA, DHEAs, cortisol/cortisone, aldosterone and homocysteine and were significantly higher in patients with NPH (p < 0.05) compared to controls. Orthogonal projections to latent structures (OPLS) model for the prediction of NPH (84.6% sensitivity) was constructed. Crucial role in the prediction play DHEA, 7α-OH-DHEA, 16α-OH-DHEA, DHEAs, aldosterone (all p<0.01), cortisol and 7-oxo-DHEA (both p<0.05) in CSF.

Conclusion: Our results highlight the laboratory changes which will contribute to early, clear and accurate diagnosis of NPH leading to suppression or attenuation of the disease.

Acknowledgement: Supported by IGA MZCR NT/12349 and NT/13369.

  1. D. Jaraj et al., Prevalence of idiopathic normal-pressure hydrocephalus, Neurology, 2014, 82(16), p. 1449-1454.
  2. C. Muller et al., Inter-conversion of 7alpha- and 7beta-hydroxy-dehydroepiandrosterone by the human 11beta-hydroxysteroid dehydrogenase type 1, J Steroid Biochem Mol Biol, 2006. 99(4-5), p. 215-222.