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Published on: November 4, 2017
CSF Biomarkers Predict Gait Outcomes in Idiopathic Normal Pressure Hydrocephalus
Jacqueline A Darrow1, Alexandria Lewis1, Seema Gulyani1
1Department of Neurology (JAD, AL, SG, KK, AR, AM), Johns Hopkins University School of Medicine; Department of Biostatistics (JW, YZ), Johns Hopkins University Bloomberg School of Public Health; Department of Neurosurgery (ML), and Department of Medicine (SY), Johns Hopkins University School of Medicine, Baltimore, MD.
Cerebrospinal fluid (CSF) biomarkers, including neurofilament light (NfL) and tau proteins, can predict long-term shunt surgery outcomes in idiopathic normal pressure hydrocephalus (iNPH). However, these biomarkers show limited ability to predict immediate response to CSF tap tests.
Area of Science:
- Neurology
- Biomarker Discovery
- Neurosurgery
Background:
- Idiopathic normal pressure hydrocephalus (iNPH) management relies on predicting shunt surgery response.
- Current biomarker assessment for iNPH patient selection is limited by small cohorts and short follow-up periods.
Purpose of the Study:
- To evaluate cerebrospinal fluid (CSF) biomarkers for predicting immediate response to CSF tap tests (TT) and long-term outcomes after shunt surgery in iNPH patients.
- To assess the predictive potential of CSF neurofilament light (NfL), beta-amyloid (Aβ), total tau (tTau), phosphorylated tau (pTau181), and leucine-rich alpha-2-glycoprotein-1 (LRG1).
Main Methods:
- CSF samples were collected from iNPH patients undergoing CSF TT.
- Biomarker levels (NfL, Aβ42, Aβ40, tTau, pTau181, LRG1) were measured using ELISA.
- Univariate and multivariate regression analyses were employed to compare biomarker prediction of immediate and long-term responses.
Main Results:
- Lower levels of NfL, pTau181, tTau, and Aβ40 predicted long-term gait improvement after shunt surgery.
- A multivariate model combining these biomarkers with the Evans index improved prediction of long-term outcomes (AUC 0.76).
- tTau, pTau181, and Aβ40 levels differed significantly between patients with and without gait improvement post-TT, but prediction of immediate TT response was modest.
Conclusions:
- A combination of CSF biomarkers can predict shunt surgery success in iNPH.
- These biomarkers have limited ability to predict immediate response to CSF tap tests.
- Abnormal CSF biomarkers in non-responders may indicate comorbid neurodegenerative conditions or a predegenerative state.
