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Open research questions in Cerebrospinal fluid and hydrocephalus

146 unresolved questions extracted from the limitations and future-work sections of 357 Cerebrospinal fluid and hydrocephalus papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Predicting shunt response in patients with iNPH remains challenging. The influence of AD co-pathology on the association between p-tau181 levels and shunt response is a challenge. The study had to account for the change in assay method from Innotest to Elecsys.

    Association between p-tau181 in cerebrospinal fluid and shunt response in patients with normal-pressure hydrocephalus · 2026 · DOI

  • Existing evidence on the association between CSF p-tau181 and shunt response is inconsistent. There is a need to identify patients eligible for surgery and predict whether an individual patient will benefit from shunt placement. The influence of AD co-pathology on the association between p-tau181 levels and shunt response is unclear.

    Association between p-tau181 in cerebrospinal fluid and shunt response in patients with normal-pressure hydrocephalus · 2026 · DOI

  • The mechanical characterization of the spinal dura mater remains challenging due to its thinness and anisotropy. There is a need for standardized protocols and data normalization when investigating soft tissue mechanics.

    Exploring the mechanical behavior of the spinal dura mater: experimental insights and measurement dilemmas · 2026 · DOI

  • Investigate the relationship between sleep and brain fluid transport in larger and more diverse populations, - Examine the effects of sleep disorders on brain diffusion parameters, - Develop new methods to quantify sleep depth and its relationship to brain function

    Regional and network patterns of sleep-depth-associated brain diffusion changes: an EEG-informed multishell diffusion MRI study · 2026 · DOI

  • The relationship between sleep-depth-associated physiological processes and regional diffusion MRI parameters is unclear. Prior studies have not investigated the interregional organization of sleep-depth-associated brain diffusion changes. The study aims to address this gap by examining regional sleep-depth associations and interregional correlation networks.

    Regional and network patterns of sleep-depth-associated brain diffusion changes: an EEG-informed multishell diffusion MRI study · 2026 · DOI

  • Further research is needed to fully understand the differences in glymphatic-related dysfunction between MS and NMOSD. Studies should investigate the relationship between glymphatic function and disease progression in MS and NMOSD. Research should focus on developing therapeutic strategies to target glymphatic dysfunction in MS and NMOSD.

    Disease-specific patterns of glymphatic-related dysfunction between multiple sclerosis and neuromyelitis optica spectrum disorder · 2026 · DOI

  • small sample size of 100 participants, - exclusion of patients with other psychiatric disorders or physical illnesses, - limited generalizability to other populations

    Modulation of depression through the neurobiological underpinnings of the glymphatic–rumination relationship · 2026 · DOI

  • investigating the relationship between glymphatic function and rumination in larger samples, - exploring the effects of enhancing glymphatic flow on depressive symptoms, - examining the role of neurotransmitters in the glymphatic-rumination relationship

    Modulation of depression through the neurobiological underpinnings of the glymphatic–rumination relationship · 2026 · DOI

  • Further studies are needed to investigate the relationship between glymphatic dysfunction and AD pathophysiology - Research on factors affecting glymphatic function in AD remains limited - Studies should explore the potential of the ALPS index as a biomarker for AD diagnosis and monitoring

    Glymphatic dysfunction associates with regional white matter hyperintensities and plasma amyloid-β burden across the Alzheimer’s disease continuum · 2026 · DOI

  • The complexity of studying multiple interacting stressors. The need for controlled experiments to isolate the effects of individual stressors. The challenge of measuring the cumulative effects of stressors on neurovascular integrity.

    Aerospace stressors and brain health in military aviators: a glymphatic–neurovascular framework · 2026 · DOI

  • causal decomposition through factorial and crossover experiments, - exposure-resolved operational research across different aircraft communities, - validation of glymphatic surrogates, - incorporation of individual differences such as sex, age, and vascular risk into prospective studies

    Aerospace stressors and brain health in military aviators: a glymphatic–neurovascular framework · 2026 · DOI

  • Differentiating true central hypothyroidism from Non-Thyroidal Illness Syndrome is a major diagnostic hurdle. The paper acknowledges the challenge of isolating pure mechanical compression of the hypothalamus from global ischemic changes. Mapping the precise real-time dynamics of the newly integrated three-interface network and localized Aquaporin-4 polarization remains a challenge.

    Hydrocephalus-induced central hypothalamic-pituitary-thyroid axis dysfunction: a conceptual framework linking ventricular distension to behavioral deficit · 2026 · DOI

  • Multicenter trials in Nigeria are needed to validate these CT-endocrine indices, - mapping the precise real-time dynamics of the newly integrated three-interface network and localized Aquaporin-4 (AQP4) polarization remains a profound challenge in human subjects

    Hydrocephalus-induced central hypothalamic-pituitary-thyroid axis dysfunction: a conceptual framework linking ventricular distension to behavioral deficit · 2026 · DOI

  • The paper identifies that the pathogenesis of CSVD remains unclear. The relationship between glymphatic system dysfunction and CSVD has not been well studied.

    Pathogenesis of Cerebral Small Vessel Disease: Role of the Glymphatic System Dysfunction · 2024 · DOI

  • Further research is needed to investigate the mechanical behavior of the spinal dura mater in different conditions. The development of standardized protocols for measuring the mechanical properties of soft tissues is necessary. Research on the effects of different measurement techniques on the estimated mechanical parameters is required.

    Exploring the mechanical behavior of the spinal dura mater: experimental insights and measurement dilemmas · 2026 · DOI

  • However, the mechanisms driving CSF flow and its oscillatory dynamics remain poorly understood.

    High frame rate in vivo two-photon microscopy to quantify murine cerebrospinal fluid flow heterogeneity · 2026 · DOI

  • Its pathogenesis remains poorly understood because it reflects the combined effects of interacting clinical insults, and because appropriate experimental models for mechanistic studies have been lacking.

    Mechanical Ventilation Impairs Glymphatic Function and Induces Delirium-Like Behavior in Mice · 2026 · DOI

  • Perivascular fibroblasts (PVFs) ensheath pial arterioles on the brain surface, yet their physiological role on the healthy cerebrovasculature remains unknown.

    Perivascular fibroblasts locally regulate the vasomotor dynamics of pial arterioles · 2026 · DOI

  • However, the role of Ki67-MIB1 values in the postoperative decision making-process of treatment, as well as the indication for adjuvant radiotherapy, remain debated.

    Central neurocytomas: Decision-making process of postoperative treatment. Lesson learned · 2026 · DOI

  • In Chile, information on hydrocephalus remains scarce from an epidemiological point of view, generating an information gap that can lead to errors in public health planning in the country.

    Defunciones por hidrocefalia en Chile entre 1997 y 2022 y caracterización de variables epidemiológicas · 2026 · DOI

  • Although endoscopic resection is now an established alternative to microsurgery, outcome data from resource-limited academic centers remain scarce.

    Endoscopic transventricular resection of third ventricular colloid cysts in a resource-limited academic setting: a prospective pilot case series · 2026 · DOI

  • The mechanisms by which cardiac diseases contribute to cognitive impairment and dementia, particularly neurodegenerative cognitive impairment, remain unclear.

    A Novel Potential Pathway Linking Cardiac Diseases and Cognitive Dysfunction: Impaired Brain Glymphatic Function · 2026 · DOI

  • However, whether ChP volume and the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index provide complementary glymphatic-related MRI information, and whether their associations with cortical thinning and cognition differ by amyloid-β (Aβ) status, remain unclear.

    Structural and diffusion MRI markers of the choroid plexus and perivascular regions are associated with Alzheimer’s disease pathology and cognition · 2026 · DOI

  • Although research shows that sleep apnea and sleep disruption are associated with PVS volumes, few studies have investigated whether sleep apnea treatment can modify this association.

    Continuous Positive Airway Pressure and Progression of Enlarged Perivascular Spaces in Adults With Obstructive Sleep Apnea · 2025 · DOI

  • Although previous studies have linked EPVS to cerebrovascular dysfunction, their relationship with AD pathology and cognitive decline remains underexplored, particularly in multiethnic cohorts.

    Association of Enlarged Perivascular Spaces With Early Serum and Neuroimaging Biomarkers of Alzheimer Disease Pathology · 2025 · DOI

Most-cited papers in Cerebrospinal fluid and hydrocephalus

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146 open questions have been extracted from the limitations and future-work passages of 357 Cerebrospinal fluid and hydrocephalus papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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