Adult hydrocephalus is a common neurologic condition with an estimated prevalence of 85 per 100,000 globally, caused by abnormal cerebrospinal fluid (CSF) accumulation within the cerebral ventricles. Subtypes include idiopathic normal pressure hydrocephalus, posthemorrhagic, postinfectious, posttraumatic, and tumor-associated forms. Its pathophysiology involves glymphatic dysfunction, neuroinflammation, vascular compromise, and impaired CSF absorption. Despite advances in treatment, significant gaps remain in understanding its epidemiology, particularly in regards to regional variability and comorbidities, alongside unresolved questions about glymphatic pathways and neurodegenerative overlap. Standardized diagnostic and therapeutic frameworks are urgently needed
Key points
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Adult hydrocephalus encompasses diverse subtypes, including idiopathic normal pressure hydrocephalus (iNPH), posthemorrhagic, postinfectious, posttraumatic, tumor-associated, and transitional forms, each with distinct epidemiology and pathophysiology.
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The condition affects 85 per 100,000 globally, with rising prevalence in aging populations, particularly iNPH, often underdiagnosed due to symptom overlap with neurodegenerative diseases.
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Key mechanisms include glymphatic dysfunction, neuroinflammation, barrier disruptions, and mechanical obstructions, reflecting complex molecular, structural, and vascular changes in pathophysiology
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Key research questions address glymphatic disruption, diagnostic and treatment variability, and whether iNPH is a distinct condition or overlaps with neurodegenerative diseases
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Unified diagnostic and therapeutic frameworks, informed by multidisciplinary research and advanced imaging, are critical to improving outcomes and addressing global disparities in care and reporting.
| AAV | adeno-associated virus |
| AHCRN | Adult Hydrocephalus Clinical Research Network |
| AQP-4 | aquaporin-4 |
| aSAH | aneurysmal subarachnoid hemorrhage |
| BBB | blood–brain barrier |
| BCB | blood–CSF barrier |
| CNS | central nervous system |
| CPe | choroid plexus epithelium |
| CSF | cerebrospinal fluid |
| DC | decompressive craniectomy |
| EVD | external ventricular drain |
| IL-6 | interleukin-6 |
| iNPH | idiopathic normal pressure hydrocephalus |
| IVH | intraventricular hemorrhage |
| NETs | neutrophil extracellular traps |
| NKCC1 | Na + -K + -Cl − |
| OR | odds ratio |
| PFTs | posterior fossa tumors |
| PHH | posthemorrhagic hydrocephalus |
| PIH | postinfectious hydrocephalus |
| PTH | posttraumatic hydrocephalus |
| PVWM | periventricular white matter |
| SAH | subarachnoid hemorrhage |
| SPAK | STE20/SPS1-related proline/alanine-rich kinase |
| TBI | traumatic brain injury |
| TBM | tuberculosis meningitis |
| TGF-β | transforming growth factor-beta |
| VP | ventriculoperitoneal |
Introduction
Hydrocephalus is a neurologic condition characterized by abnormal cerebrospinal fluid (CSF) accumulation within the brain due to disruptions in CSF production, flow, or absorption. This imbalance causes ventricular enlargement, intracranial pressure changes, and significant neurologic sequalae. With the aging global population and improvements in neuroimaging techniques, the prevalence of adult hydrocephalus is rising, underscoring its clinical and public health importance.
Adult hydrocephalus encompasses a heterogenous group of conditions, traditionally classified into obstructive (noncommunicating) and communicating types based on whether an anatomic obstruction of CSF flow is present. Among individuals aged over 60 years, idiopathic normal pressure hydrocephalus (iNPH) is the most common subtype, characterized by a triad of gait disturbance, cognitive decline, and urinary incontinence. Other subtypes such as hydrocephalus ex vacuo, adult low-pressure hydrocephalus, long-standing overt ventriculomegaly in adults, syndrome of hydrocephalus in young and middle-aged adults, and adult previously unrecognized congenital hydrocephalus, contribute to the variability in epidemiologic estimates.
Variability in classification and diagnostic practices complicates epidemiologic studies, prompting recent efforts to establish unified classification systems. , To promote consistency, this review adopts the Adult Hydrocephalus Clinical Research Network (AHCRN) framework, which categorizes adult hydrocephalus into iNPH, transitional hydrocephalus, acquired hydrocephalus, and unrecognized congenital hydrocephalus. While this approach enhances clarity, it does not dismiss earlier frameworks or their contributions.
The pathophysiology of hydrocephalus involves multifaceted mechanisms, including CSF production–absorption imbalances, glymphatic dysfunction, neuroinflammation, and structural brain changes. Although many mechanisms are shared across subtypes, unique etiologies such as trauma, infection, or neoplasms influence disease progression and treatment strategies. ,
This review synthesizes current evidence on the epidemiology and pathophysiology of adult hydrocephalus, emphasizing its subtypes, prevalence, and risk factors. By identifying research gaps and proposing directions for innovation, it aims to advance understanding and inform strategies for clinical care and resource allocation.
Discussion
Epidemiology
General trends and regional variability
Hydrocephalus in adults is an increasingly global health concern, with a worldwide prevalence estimated at approximately 85 in 100,000 individuals. Among adults aged 19 to 64 years, the prevalence is lower, around 11 per 100,000, but rises sharply with age. The prevalence in older populations is striking, reaching 175 per 100,000 in those aged 65 to 80 years and up to 400 per 100,000 among individuals aged over 80 years. , These trends largely reflect advancements in diagnostic capabilities, particularly for iNPH, and the identification of compensated congenital hydrocephalus.
Significant regional variability characterizes the epidemiology of hydrocephalus, influenced by health care infrastructure, diagnostic practices, and the prevalence of contributing conditions. In high-income regions, iNPH constitutes a major burden, affecting 1% to 3% of the elderly population. In contrast, resource-limited settings report higher rates of postinfectious hydrocephalus (PIH), often linked to bacterial or tuberculous meningitis. Among younger adults, transitional hydrocephalus arising from childhood hydrocephalus and posttraumatic hydrocephalus (PTH) resulting from head injuries are more common.
The reported incidence and prevalence of hydrocephalus are heavily influenced by variability in diagnostic criteria, access to neuroimaging, health care availability, and reporting protocols. This variability underscores the need for standardization to enhance epidemiologic accuracy and guide-targeted interventions.
Subtype-specific epidemiology
Idiopathic normal pressure hydrocephalus
iNPH affects 1% to 3% among community-dwelling elderly individuals, globally, with prevalence sharply increasing with age. , Age-stratified data indicate iNPH occurs in 0.2% of individuals aged 70 to 79 years and rises to 6% in those aged over 80 years. Corresponding incidence rates range from 10 per 100,000 individuals aged 65 to 74 years to 30 per 100,000 in those aged 85 years or older. , According to the AHCRN, iNPH constitutes approximately 39% of all adult hydrocephalus cases, with an average age at diagnosis of 77 years.
Epidemiologic trends vary significantly by region due to differences in health care infrastructure, diagnostic criteria, and demographic profiles. Japan reports an annual incidence of 10 per 100,000 and a prevalence of 22 per 100,000, , while Norway and Spain report incidences of 6 per 100,000 and 3 per 100,000, respectively. In Sweden, the prevalence of iNPH is 1.5% among individuals aged 70 years, with higher rates observed in men (2%) compared to women (1%).
Population-based radiological studies indicate that ventriculomegaly (Evans Index >0.3) is present in up to 36% of elderly individuals, many of whom remain asymptomatic and are classified as asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM). Longitudinal studies suggest that approximately 11% of individuals with AVIM develop symptomatic iNPH within 3 years. This highlights a substantial pool of undiagnosed or preclinical cases, likely due to symptom overlap with neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.
Acquired hydrocephalus
Posthemorrhagic hydrocephalus
Posthemorrhagic hydrocephalus (PHH) is a common complication of intracranial hemorrhages, including subarachnoid hemorrhage (SAH), intraventricular hemorrhage (IVH), and intracerebral hemorrhage. Incidence rates vary widely, reflecting differences in patient populations, hemorrhage severity, and diagnostic criteria. PHH occurs in 10% to 65% of aneurysmal subarachnoid hemorrhage (aSAH) cases, and in 51% to 89% of IVH cases. The high incidence of PHH in IVH underscores the significant risk posed by intraventricular blood burden. , , Regional and institutional differences in diagnostic practices and treatment protocols further contribute to variability in reported rates.
Temporal trends provide additional insights into PHH epidemiology. Acute PHH, occurring within 72 hours of hemorrhage, is reported in 15% to 58% of aSAH cases and typically necessitates temporization with an external ventricular drain (EVD). , Among these patients, 70% progress to chronic hydrocephalus requiring permanent shunting. Risk factors for PHH development and shunt dependency include high clot burden, particularly in the basal cisterns, high SAH grade, posterior circulation aneurysmal rupture, advanced age, hypertension, prolonged EVD (typically >14 days; odds ratio [OR] 6.21), and high daily CSF output (>78 mL/d; OR 1.004 per mL increase). , ,
Angiogram-negative SAH, particularly nonperimesencephalic (non-perimesencephalic hemorrhage [PMH]) cases, are associated with an elevated risk of hydrocephalus and shunt dependency. Non-PMH cases show a hydrocephalus incidence of 28.3% compared to 9.7% in PMH and a shunt dependency rate of 11.2% versus 2.6%, respectively.
Postinfectious hydrocephalus
PIH remains a serious complication of central nervous system (CNS) infections, with significant regional variability influenced by causative pathogens and health care infrastructure. In low-income and middle-income countries, tuberculosis meningitis (TBM) and neurocysticercosis are leading causes of PIH. Conversely in high-income regions, bacterial meningitis—predominantly from pathogens like Streptococcus pneumoniae and Escherichia coli— accounts for most cases. Systematic reviews report that hydrocephalus requiring permanent CSF diversion occurs in up to 7% of patients with pneumococcal meningitis. Listeria monocytogenes , though less common, leads to hydrocephalus in approximately 15% of infections.
TBM is particularly burdensome in high-prevalent regions such as sub-Saharan Africa and Southeast Asia. Hydrocephalus affects nearly 65% of patients at diagnosis, with an additional 10% developing hydrocephalus during the treatment of TBM. , The high prevalence is attributed to the extensive inflammatory response and thick basal exudates that obstruct the basal cisterns and ventricular outlets. In settings with high human immunodeficiency virus prevalence, coinfection significantly amplifies the risk and worsens outcomes of PIH.
Posttraumatic hydrocephalus
PTH is a frequent and severe complication of traumatic brain injury (TBI), with reported incidence rates ranging from 1% to 45%, reflecting variability in diagnostic criteria, study populations, follow-up durations, and regional differences. Among patients with severe TBI admitted to intensive care units, incidence is generally reported between 2% and 20%, with a median time to diagnosis of 102 days postdischarge. A Swedish study identified ventriculomegaly in 46% of patients with TBI, with 3.5% requiring ventriculoperitoneal (VP) shunting, predominantly within the first year after injury.
The type and severity of TBI are key predictors of PTH development. Decompressive craniectomy (DC), commonly performed to alleviate intracranial pressure, is associated with PTH incidences ranging from 10% to 35%. , DC alters CSF dynamics, significantly increasing hydrocephalus risk. Other important risk factors of PTH include traumatic SAH (OR 3.7), IVH, and midline brain shift (OR 1.9). 37 PTH is more commonly observed in older adults and those with severe TBI, as indicated by lower Glasgow Coma Scale scores at admission. Despite its clinical significance, PTH remains underdiagnosed. Many cases are misclassified as hydrocephalus ex vacuo, where ventricular enlargement results from brain atrophy, or are overlooked due to symptom overlap with other post-TBI sequelae.
Tumor-associated hydrocephalus
Tumor-associated hydrocephalus exhibits variable prevalence depending on tumor type, location, and behavior. Discrepancies in reported rates are also influenced by differences in diagnostic thresholds, treatment protocols, and study methodologies. Supratentorial malignant gliomas are associated with hydrocephalus in approximately 10% of cases, while rates in giant pituitary adenomas, petroclival meningiomas, and vestibular schwannomas are approximately 8%, 13%, and 15%, respectively. Tumors infiltrating the ventricular system significantly increase the risk of postoperative hydrocephalus, with an incidence of 19%. Posterior fossa tumors (PFTs) have particularly high rates, with preoperative hydrocephalus affecting approximately 20% of patients. , Postoperatively, acute hydrocephalus occurs in about 7% of PFT cases, while persistent hydrocephalus requiring VP shunting is observed in approximately 3% of patients. Additional factors that increase the risk of hydrocephalus include subtotal tumor resection, infiltration of the cerebral aqueduct (OR 9.8), and postoperative hemorrhage, which dramatically increases the odds (OR 67).
Transitional hydrocephalus
Transitional hydrocephalus, which encompasses Adults who were treated for childhood-onset hydrocephalus, represents approximately 17% of adult hydrocephalus cases, as reported by the AHCRN. This group is characterized by a younger demographic, with an average age of 33 years and presents distinct challenges reflecting the lifelong, evolving nature of hydrocephalus. The primary etiologies of childhood-onset hydrocephalus in this population include myelomeningocele (34%), aqueductal stenosis (15%), IVH of prematurity (9%), and PIH (7%).
Transitional hydrocephalus underscores the need for continuity of care between pediatric and adult neurosurgical services. Longitudinal registries and enhanced surveillance systems are essential for improving understanding of their clinical trajectories, optimizing resource allocation, and identifying long-term complications.
Pathophysiology
Overview of physiology
Understanding the physiology of the ventricular system, choroid plexus, and CSF barriers is fundamental for contextualizing the pathophysiology of adult hydrocephalus. This knowledge is also essential for developing targeted interventions to restore CSF homeostasis and mitigate hydrocephalus progression.
Cerebrospinal fluid production and flow
CSF is a critical component of CNS homeostasis, providing mechanical protection, nutrient delivery, and metabolic waste clearance. While derived as an ultrafiltrate of plasma, CSF is distinct in composition, characterized by higher chloride and lower potassium and calcium concentrations ( Table 1 ). , Its protein content is significantly lower than plasma and exhibits a cranio-caudal gradient, with higher protein levels in the lumbar cisterns compared to ventricular CSF.
| CSF | Plasma | |
|---|---|---|
| Na + (mM/L) | 147 | 153 |
| Cl − (mM/L) | 113 | 110 |
| K + (mM/L) | 2.9 | 4.7 |
| Ca 2+ (mM/L) | 1.1 | 1.3 |
| Protein (g/dL) | 0.03 | 7 |
The classic “bulk flow” model describes CSF production by the choroid plexus, unidirectional flow through the ventricular system, and absorption into the venous circulation via arachnoid granulations ( Fig. 1 ). However, emerging research underscores a more intricate bidirectional flow, glymphatic interactions, and extracranial lymphatic pathways. These insights have refined our understanding of CSF dynamics, revealing complexity beyond the classic model.
Blood–cerebrospinal fluid barrier
The choroid plexus is a specialized tissue responsible for CSF production, solute transport, and immune system regulation. Composed of a network of connective tissue and fenestrated capillaries surrounded by cuboidal epithelial cells, it forms the blood–CSF barrier. This barrier ensures selective permeability, mediated by tight and adherens junctions. , CSF production relies on transporters such as aquaporins, Na + -K + -ATPase, Cl − -HCO 3 − , Na + -K + -Cl − (NKCC1), and glucose transporter 1, which create osmotic gradients essential for water movement into the ventricles ( Fig. 2 ). The choroid plexus produces approximately 500 mL of CSF daily, accounting for 70% to 80% of total CSF volume. Beyond secretion, it plays vital roles in maintaining CNS homeostasis through solute transport and immune surveillance, emphasizing its multifunctionality in health and disease ( Fig. 3 ).
Brain–cerebrospinal fluid barrier
The ependymal layer, lining the ventricular system, is a crucial component of the brain–CSF barrier. This monolayer of multiciliated epithelial cells is held together near its apical surface by junctional proteins, such as N-cadherin and other cell adhesion molecules. Coordinated ciliary movement facilitates CSF circulation and debris clearance, underscoring its role in maintaining CSF dynamics and CNS homeostasis. Additionally, the ependymal layer protects the underlying subependymal gray and white matter, by serving as a barrier against CSF-borne toxins.
Ependymal disruption, caused by inflammatory, ischemic, or mechanical insults, contributes to the pathophysiology of hydrocephalus. Damage to this barrier impairs CSF flow, exacerbates neuroinflammation, and promotes periventricular tissue injury. These processes highlight the dual roles of the ependymal layer in facilitating CSF flow and safeguarding CNS architecture, central to both normal physiology and disease mechanisms.
General pathophysiological mechanisms
Neuroinflammation and impaired cerebrospinal fluid absorption
Impaired CSF absorption is a defining feature of communicating hydrocephalus, often linked to dysfunction at the arachnoid granulations. This dysfunction is typically triggered by CNS insults such as hemorrhage, infection, or trauma, which induce inflammation, fibrosis, and scarring in the subarachnoid space. Transforming growth factor-beta (TGF-β) is a key mediator in these processes, promoting fibrotic changes by modulating glial fibrillary acidic protein and connective tissue growth factors. , Elevated TGF-β levels, commonly observed in the CSF of patients with PHH, promote fibrosis in the subarachnoid space and ependymal lining, impairing CSF absorption capacity and disrupting normal flow dynamics. ,
Emerging research has identified neutrophil extracellular traps (NETs) as another contributor to impaired CSF absorption. NETs are web-like structures composed of extracellular DNA and histones, released during inflammatory responses, which have been shown to obstruct meningeal lymphatic vessels, impeding CSF drainage and exacerbating neuroinflammation. , Preclinical studies demonstrate that degrading NETs with therapeutic agents such as DNase-1, can enhance CSF drainage and reduce inflammation, highlighting a promising potential intervention for hydrocephalus.
The interplay of multiple mechanisms, including TGF-β-driven fibrosis and NET-mediated obstruction, amplifies neuroinflammatory cascades and perpetuates impaired CSF absorption. These synergistic processes exacerbate hydrocephalus progression and associated neurologic dysfunction.
Impaired lymphatic and glymphatic drainage
Recent advances in the understanding of CSF absorption have expanded beyond the traditional focus on arachnoid granulations to include critical roles of the extracranial lymphatic and glymphatic systems. These insights have reshaped the conceptual framework of CSF homeostasis and provided new perspectives on the pathophysiology of adult hydrocephalus. Animal studies demonstrate that CSF drains into cervical and spinal lymphatic systems via pathways associated with cranial and spinal nerves. The cribriform plate, associated with olfactory nerve drainage, has also been identified as a key conduit for CSF outflow. Disruption of these lymphatic pathways elevates intracranial pressure and impairs CSF clearance, underscoring their essential roles alongside venous absorption. ,
The glymphatic system, a complementary mechanism, is integral to CSF circulation and the clearance of metabolic waste. This system is particularly active during non-REM sleep and involves the movement of CSF from periarterial spaces into the brain’s interstitial fluid, facilitating the removal of neurotoxic metabolites ( Fig. 4 ). These byproducts are subsequently transported to perivenous spaces and meningeal lymphatic vessels, eventually draining into the deep cervical lymph nodes. Disruption of glymphatic clearance has been implicated in hydrocephalus development. In iNPH, impaired glymphatic function contributes to the accumulation of neurotoxic metabolites such as amyloid-beta and tau proteins, exacerbating neuroinflammation and disease progression. , ,
