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Open research questions in Cerebrospinal fluid and hydrocephalus

45 unresolved questions extracted from the limitations and future-work sections of 218 Cerebrospinal fluid and hydrocephalus papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Background: The cerebrospinal fluid tap test (CSF-TT) is widely used as an ancillary test to identify patients with idiopathic Normal Pressure Hydrocephalus (iNPH) for surgical management; however, its diagnostic utility remains unclear.

    Diagnostic accuracy of CSF tap-test parameters in predicting shunt responsiveness in normal pressure hydrocephalus: a cohort study · 2026 · DOI

  • Emerging evidence suggests that the choroid plexus (ChP) and the locus coeruleus (LC) are involved in cerebrospinal fluid dynamics and norepinephrine regulation, respectively, but their longitudinal alterations and interrelationships in PD have not been systematically examined.

    Complementary choroid plexus and locus coeruleus dysfunction in Parkinson's disease progression · 2026 · DOI

  • Parkinsons disease (PD) is a progressive neurodegenerative disorder commonly accompanied by cognitive decline, yet the mechanisms linking disrupted brain homeostasis to progressive cognitive impairment remain unclear.

    Complementary choroid plexus and locus coeruleus dysfunction in Parkinson's disease progression · 2026 · DOI

  • Whether this could be a cause or consequence of the disease remains uncertain. Although a previous MRI study suggested that CSF production is not increased in iNPH, this evidence is limited 1 3Neuroradiology Table 1 Demographics and imaging features.

    Increased free interstitial fluid in the normal appearing brain in idiopathic normal pressure and post-hemorrhagic hydrocephalus despite unchanged choroid plexus size · 2026 · DOI

  • Our findings suggest that determination of intraoperative ICP parameters is feasible, safe and might ultimately prove helpful in improving patient selection for ETV/CPC, warranting further investigation in larger cohorts.

    Intraoperative effects of ETV and CPC on intraventricular pressure and pulsation amplitude: A preliminary investigation of the hydrodynamic model of infant hydrocephalus · 2026 · DOI

  • Despite the widespread use of magnetic resonance imaging (MRI), quantitative morphometric criteria for the assessment of mass effect severity remain insufficiently standardised.

    MORPHOMETRIC CRITERIA FOR THE ASSESSMENT OF MASS EFFECT IN INTRACRANIAL SPACE-OCCUPYING LESIONS BASED ON MAGNETIC RESONANCE IMAGING DATA · 2026 · DOI

  • Recently, BOLD fMRI-based methods have emerged for assessing pulsatility, however their interpretability is limited because the relation between estimated pulsatility indices (PI) and vascular anatomy and physiology remains poorly understood.

    Cerebrovascular pulsatility differs across vascular compartments and is altered by hypercapnic stimuli: a BOLD fMRI study · 2026 · DOI

  • Brain vasomotor, respiratory, and cardiac pulsations are thought to drive glymphatic clearance during sleep, yet OSA's effect on these pulsations remains poorly understood.

    Obstructive Sleep Apnea Syndrome Disrupts Glymphatic-Related Physiological Brain Pulsations · 2026 · DOI

  • While lower volumes of PVS in the forebrains white matter and basal ganglia have been also demonstrated in preterm-born neonates, the long-term trajectory of PVS after premature birth remains unclear.

    Higher PVS volume in adults born very preterm · 2026 · DOI

  • Introduction: Perivascular spaces (PVS) support brain homeostasis through metabolite delivery and waste clearance, yet the genetic determinants of PVS morphology during childhood remain unknown.

    Genetic Architecture of Perivascular Space Morphology in the Pediatric Brain · 2026 · DOI

  • Reduced BOLD-CSF coupling has been previously reported in Parkinsons disease but its characterization in dementia with Lewy bodies, regional specificity and relevance to shared neuropsychiatric symptoms remain unclear.

    Impaired cerebrovascular-cerebrospinal fluid coupling is associated with non-motor features of Lewy body disease · 2026 · DOI

  • The limitation of this study is that it is a retrospective and a single centre study. A larger sample, multicentre and prospective study could improve quality and generaliz- ability. The lack of neurological, functional, and/or devel- opmental outcome assessment among these patients is also a recognized limitation of this study.

    The outcomes of ventriculoperitoneal shunt insertion for paediatric hydrocephalus in a resource-limited setting: a Nigerian tertiary institution 5-year experience · 2026 · DOI

  • The paper references tissue biorepository infrastructure for clinical translation but does not specify standardized protocols for longitudinal immune profiling of perioperative neuroimmune changes in neurosurgical patients. Comparative characterization of macrophage subsets at the meningeal margin across different surgical procedures and timepoints post-resection is needed to establish mechanistic benchmarks.

    Neurosurgery as an immune anchor point: a translational framework for perioperative immunoengineering · 2026 · DOI

  • The framework lacks empirical evidence on how acute systemic inflammatory responses (LPS-induced perivascular CSF distribution impairment) translate to disruption of the meningeal lymphatic-venous axis in neurosurgical patients. Mechanistic studies using aquaporin-4 dysfunction models in the context of surgical stress response are needed to establish causal relationships between surgical injury and immune privilege breakdown.

    Neurosurgery as an immune anchor point: a translational framework for perioperative immunoengineering · 2026 · DOI

  • The paper identifies meningeal immunity and neuroinflammation-associated neurotoxicity from immune checkpoint inhibitor therapy but does not specify mechanistic predictors for identifying patients at high risk of severe neurological adverse events. Biomarker profiling of clonally expanded effector CD4+ cytotoxic T lymphocytes and their correlation with perioperative autonomic nervous system imbalance requires prospective validation in neurosurgical cohorts.

    Neurosurgery as an immune anchor point: a translational framework for perioperative immunoengineering · 2026 · DOI

  • The translational framework does not address how blood-brain barrier dysfunction varies across different neurosurgical procedures and how this impacts the pharmacokinetics of intratumoral immunotherapeutic administration in glioma resection versus vascular neurosurgery. Comparative pharmacodynamic studies are needed to determine optimal drug delivery strategies for choroid plexus-mediated immune responses in post-operative CNS patients.

    Neurosurgery as an immune anchor point: a translational framework for perioperative immunoengineering · 2026 · DOI

  • The paper proposes neurosurgery as an immune anchor point for perioperative immunoengineering but lacks specific protocols for timing and dosing of immunotherapeutic interventions relative to surgical resection in different neurosurgical contexts (brain tumors vs. hemorrhagic stroke vs. aneurysmal subarachnoid hemorrhage). Quantitative frameworks are needed to characterize how surgical trauma window affects meningeal lymphatic function and glymphatic clearance in distinct pathological settings.

    Neurosurgery as an immune anchor point: a translational framework for perioperative immunoengineering · 2026 · DOI

  • The segmentation tool should be applied to investigate MLV-containing perisinusoidal tissue under various pathological conditions where brain waste clearance systems are compromised, such as in Alzheimer's disease, Parkinson's disease, and traumatic brain injury, to characterize how glymphatic dysfunction correlates with perisinusoidal tissue morphology.

    Artificial intelligence-based segmentation of perisinusoidal tissue along the superior sagittal sinus in human brain magnetic resonance imaging · 2026 · DOI

  • The AI-based segmentation model requires validation across larger and more diverse datasets to confirm its robustness and generalizability beyond the current cohort. Specifically, the model's performance on perisinusoidal tissue segmentation needs testing across different MRI scanner types, field strengths, and acquisition protocols to establish clinical applicability.

    Artificial intelligence-based segmentation of perisinusoidal tissue along the superior sagittal sinus in human brain magnetic resonance imaging · 2026 · DOI

  • OBJECTIVE: Choroid plexus (CP) is a key regulator in cerebrospinal fluid production, but its contribution to glymphatic clearance function and association with white matter hyperintensity (WMH) remains unclear.

    Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment · 2023 · DOI

  • The possible functional components of the ependyma and choroid plexus morphology of the AGR are discussed and thus provide a baseline for further research on the AGR brain.

    Ultrastructural Morphology of the Ependyma and Choroid Plexus in the African Giant Rat ( <i>Cricetomys gambianus</i> ) · 2021 · DOI

  • Our findings are contradictory to the classic hypothesis of CSF physiology based on secretion, circulation, and absorption of CSF, which states that the impairment of CSF circulation through the aqueduct of Sylvius inevitably leads to a hypertensive hydrocephalus development involving the third and the lateral ventricle.

    Long lasting near-obstruction stenosis of mesencephalic aqueduct without development of hydrocephalus – case report · 2014 · DOI

  • No research has been identified looking directly at balance changes in patients with iNPH following TT or VP shunt insertion and the efficacy of objective gait assessments in this patient population has not been evaluated.

    Idiopathic normal pressure hydrocephalus, what is the physiotherapist’s role in assessment for surgery? · 2013 · DOI

  • The relationship between O-CPECs and other CPEC pathologies in humans, such as Biondi body (BB) amyloid inclusions, remains poorly defined.

    Age-associated oncocytic transformation correlates with an increased prevalence of small multiple Biondi body inclusions in human choroid plexus epithelial cells · 2026 · DOI

  • The Automatic Segmentation of Choroid Plexus (ASCHOPLEX), a deep learning framework originally trained on healthy controls and multiple sclerosis cohorts, has not been systematically evaluated in neurodegenerative populations.

    Automatic segmentation of choroid plexus using deep learning across neurodegenerative diagnoses in the multi-site COMPASS-ND Study · 2026 · DOI

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45 open questions have been extracted from the limitations and future-work passages of 218 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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