Popular circulation theory of hydrocephalus assumes that the brain is impermeable to cerebrospinal fluid (CSF), and is therefore incapable of absorbing the CSF accumulating within the ventricles. However, the brain parenchyma is permeable to water due to the presence of specific ion channels as well as aquaporin channels. Thus, the movement of water into and out of the ventricles may be determined by the osmotic load of the CSF. If osmotic load determines the aqueous content of CSF in this manner, it is reasonable to hypothesize that hydrocephalus may be precipitated by pathologies and/or insults that produce sustained elevations of osmotic content within the ventricles.

No abstract available

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.

Normal-pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia and urinary incontinence. A critical review of the concept, pathophysiology, diagnosis, and treatment of both idiopathic and secondary NPH was conducted. We searched Medline and PubMed databases from January 2012 to December 2018 using the keywords "normal-pressure hydrocephalus" / "idiopathic normal-pressure hydrocephalus" / "secondary normal-pressure hydrocephalus" / "NPH" / "ventriculoperitoneal shunt". The initial search produced 341 hits. After careful selection, a total of 54 articles were chosen and additional relevant studies were included during the process of writing this article. NPH is an important cause of potentially reversible dementia, frequent falls and recurrent urinary infections in the elderly. The clinical and imaging features of NPH may be incomplete or nonspecific, posing a diagnostic challenge for medical doctors and often requiring expert assessment to minimize unsuccessful surgical treatments. Recent advances resulting from the use of non-invasive MRI methods for quantifying cerebral blood flow, in particular arterial spin-labeling (ASL), and the frequent association of NPH and obstructive sleep apnea (OSA), offer new avenues to understand and treat NPH.

Chronic communicating hydrocephalus is a significant health problem affecting up to 20% of survivors of spontaneous subarachnoid hemorrhage (SAH). The development of new treatment strategies is hampered by the lack of well characterized disease models. This study investigated the incidence of chronic hydrocephalus by evaluating the temporal profile of intracranial pressure (ICP) elevation after SAH, induced by endovascular perforation in rats. Twenty-five adult male Sprague-Dawley rats (260-320 g) were subjected to either endovascular perforation or sham surgery. Five animals died after SAH induction. At 7, 14 and 21 days after surgery ICP was measured by stereotaxic puncture of the cisterna magna in SAH (n=10) and SHAM (n=10) animals. On day 21 T-maze test was performed and the number of alterations and latency to decision was recorded. On day 23, samples were processed for histological analyses. The relative ventricle area was evaluated in coronal Nissl stained sections. On day 7 after surgery all animals showed normal ICP. The absolute ICP values were significantly higher in SAH compared to SHAM animals on day 21 (8.26±4.53 mmHg versus 4.38±0.95 mmHg) but not on day 14. Observing an ICP of 10 mmHg as cut-off, 3 animals showed elevated ICP on day 14 and another animal on day 21. The overall incidence of ICP elevation was 40% in SAH animals. On day 21, results of T-maze testing were significantly correlated with ICP values, i.e. animals with elevated ICP showed a lower number of alterations and a delayed decision. Histology yielded a significantly higher (3.59 fold increased) relative ventricle area in SAH animals with ICP elevation compared to SAH animals without ICP elevation. In conclusion, the current study shows that experimental SAH leads to chronic hydrocephalus, which is associated with ICP elevation, behavioral alterations and ventricular dilation in about 40% of SAH animals.

As magnetic resonance imaging (MRI) signs of normal pressure hydrocephalus (NPH) may precede clinical symptoms we sought to evaluate an algorithm that automatically detects this pattern.

While normal-pressure hydrocephalus (NPH) is most commonly diagnosed in older adulthood, a significant body of literature has accumulated over half a century documenting the clinical phenomenon of an NPH-like syndrome in pediatric patients. As in adult NPH, it is likely that pediatric NPH occurs due to a heterogeneous array of developmental, structural, and neurodegenerative pathologies, ultimately resulting in aberrant cerebrospinal fluid (CSF) flow and distribution within and around the brain. In this review, we aimed to systematically survey the existing clinical evidence supporting the existence of a pediatric form of NPH, dating back to the original recognition of NPH as a clinically significant subtype of communicating hydrocephalus. Leveraging emergent trends from the old and more recent published literature, we then present a modern characterization of pediatric NPH as a disorder firmly within the same disease spectrum as adult NPH, likely with overlapping etiology and pathophysiological mechanisms. Exemplary cases consistent with the diagnosis of pediatric NPH selected from the senior author's neurosurgical practice are then presented alongside the systematic review to aid in discussion of the typical clinical and radiographic manifestations of pediatric NPH. Common co-morbidities and modern surgical treatment options are also described.

Nearly 700,000 adults in the US have normal pressure hydrocephalus (NPH), but it is often misdiagnosed as Alzheimer's or Parkinson's disease. In fact, a small percentage of people with the disease are properly diagnosed. NPH presents classically with a triad of symptoms: ataxic gait, dementia, and urinary incontinence. Diagnosis and treatment are provided together through a lumbar puncture. However, the only effective treatment that exists is a shunt insertion, which is a highly invasive procedure with uncertain responsiveness. As NPH is primarily diagnosed in those in advanced ages (60s and 70s), adjunctive treatment modalities should be further studied. Here we present a case of a patient diagnosed by a neurosurgeon and neurologist with NPH and a candidate for a shunt insertion whose symptoms substantially improved with one month of osteopathic manipulative treatment. Osteopathic considerations and literature are also reviewed in the broader context of craniosacral treatment.

Hydrocephalus is a common and major complication that affects outcome after intraventricular hemorrhage (IVH). While aging impacts the occurrence of hydrocephalus in patients with IVH this and the underlying mechanisms have received little attention. The present investigation, therefore, studied the impact of aging on hydrocephalus after IVH in a rat model.

Hydrocephalus is especially prevalent in countries with limited resources, where its treatment is still a challenge. However, long-term neuropathological changes in untreated hydrocephalus remain largely unexplored. The present study looks at cortical parenchyma and neuroinflammation in acquired, chronic hydrocephalus. Intracisternal kaolin injections were performed in 3-week-old rats, followed by -1, 4- and 8-week survival; matched control rats received saline injections. Ventriculomegaly has been previously reported to stabilize by the third week in this model. Single and triple immunocytochemical approaches were used to highlight neurones, astrocytes, microglia, and the pro-inflammatory cytokine interleukin (IL)-1β in the parietal cortex, utilizing cell counts and densitometry. Microglial protein ionized calcium binding adaptor molecule 1 (Iba1) and IL-1β expressions were monitored with Western blotting in the parietal cortex and hippocampus. In the parietal cortex, which showed progressive disruption of cytoarchitecture, neuronal density was significantly increased at 8weeks post-induction but not at earlier time points, indicating on-going cortical damage in chronic hydrocephalus. Astrocyte and microglia hypertrophy, and Iba1 expression indicated glial cell activation which peaked at 4weeks. IL-1β expression also peaked at 4weeks and was then down-regulated. Overall the findings indicate that neuroinflammatory features build up in the first month after hydrocephalus induction implicating marked IL-1β upregulation. The data also show that astrocytes are the main source of IL-1β in this disorder.

We report nine cases of obstructive or communicating hydrocephalus among 64 infants and children with intraspinal neoplasms. There were three intramedullary, four intradural, and two extradural tumors. Although four patients had papilledema, and five myelograms revealed total block, the total CSF protein level was not always elevated in the fluid above the intraspinal lesion. Analysis of these nine cases permits several different pathogenetic considerations of hydrocephalus associated with intraspinal tumors. The high incidence (14%) of this coexistent syndrome might be a characteristic of intraspinal neoplasms in infants and young children.

No abstract available

Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.

Tumor-associated hydrocephalus (TAH) is a common and lethal complication of brain metastases. Although other factors beyond mechanical obstructions have been suggested, the exact mechanisms are unknown. Using single-nucleus RNA sequencing and spatial transcriptomics, we find that a distinct population of mast cells locate in the choroid plexus and dramatically increase during TAH. Genetic fate tracing and intracranial mast-cell-specific tryptase knockout showed that choroid plexus mast cells (CPMCs) disrupt cilia of choroid plexus epithelia via the tryptase-PAR2-FoxJ1 pathway and consequently increase cerebrospinal fluid production. Mast cells are also found in the human choroid plexus. Levels of tryptase in cerebrospinal fluid are closely associated with clinical severity of TAH. BMS-262084, an inhibitor of tryptase, can cross the blood-brain barrier, inhibit TAH in vivo, and alleviate mast-cell-induced damage of epithelial cilia in a human pluripotent stem-cell-derived choroid plexus organoid model. Collectively, we uncover the function of CPMCs and provide an attractive therapy for TAH.

We conducted PrediXcan analysis of hydrocephalus risk in ten neurological tissues and whole blood. Decreased expression of MAEL in the brain was significantly associated (Bonferroni-adjusted p < 0.05) with hydrocephalus. PrediXcan analysis of brain imaging and genomics data in the independent UK Biobank (N = 8,428) revealed that MAEL expression in the frontal cortex is associated with white matter and total brain volumes. Among the top differentially expressed genes in brain, we observed a significant enrichment for gene-level associations with these structural phenotypes, suggesting an effect on disease risk through regulation of brain structure and integrity. We found additional support for these genes through analysis of the choroid plexus transcriptome of a murine model of hydrocephalus. Finally, differential protein expression analysis in patient cerebrospinal fluid recapitulated disease-associated expression changes in neurological tissues, but not in whole blood. Our findings provide convergent evidence highlighting the importance of tissue-specific pathways and mechanisms in the pathophysiology of hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH), the most common type of adult-onset hydrocephalus, is a potentially reversible neuropsychiatric entity characterized by dilated ventricles, cognitive deficit, gait apraxia, and urinary incontinence. Despite its relatively typical imaging features and clinical symptoms, the pathogenesis and pathophysiology of iNPH remain unclear. In this review, we summarize current pathogenetic conceptions of iNPH and its pathophysiological features that lead to neurological deficits. The common consensus is that ventriculomegaly resulting from cerebrospinal fluid (CSF) dynamics could initiate a vicious cycle of neurological damages in iNPH. Pathophysiological factors including hypoperfusion, glymphatic impairment, disturbance of metabolism, astrogliosis, neuroinflammation, and blood-brain barrier disruption jointly cause white matter and gray matter lesions, and eventually lead to various iNPH symptoms. Also, we review the current treatment options and discuss the prospective treatment strategies for iNPH. CSF diversion with ventriculoperitoneal or lumboperitonealshunts remains as the standard therapy, while its complications prompt attempts to refine shunt insertion and develop new therapeutic procedures. Recent progress on advanced biomaterials and improved understanding of pathogenesis offers new avenues to treat iNPH.

To evaluate the correlation between the distance of craniectomy from the midline and hydrocephalus after DC.

The cerebral cortex may be compressed in hydrocephalus and some experiments suggest that movement of extracellular substances through the cortex is impaired. We hypothesized that the extracellular compartment is reduced in size and that the composition of the extracellular compartment changes in rat brains with kaolin-induced hydrocephalus.

To investigate if visuomotor coordination of hand movements is impaired in patients with normal pressure hydrocephalus (NPH) identified by dedicated testing procedures.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients. Two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of iNPH patients and were significantly enriched 6.6-fold and 2.7-fold, respectively, when compared to the general population. Cwh43 modifies the lipid anchor of glycosylphosphatidylinositol-anchored proteins. Mice heterozygous for CWH43 deletion appeared grossly normal but displayed hydrocephalus, gait and balance abnormalities, decreased numbers of ependymal cilia, and decreased localization of glycosylphosphatidylinositol-anchored proteins to the apical surfaces of choroid plexus and ependymal cells. Our findings provide novel mechanistic insights into the origins of iNPH and demonstrate that it represents a distinct disease entity.