Application of novel non-invasive ophthalmic imaging to visualize peripapillary wrinkles, retinal folds and peripapillary hyperreflective ovoid mass-like structures associated with elevated intracranial pressure.

Background: Elevated intracranial pressure (ICP) is a serious and potentially life-threatening condition, for which clinically useful non-invasive measures have been elusive, in some cases due to their inadequate sensitivity and specificity. Our aim was to evaluate novel non-invasive ophthalmic imaging of selected pathological features seen in elevated ICP, namely peripapillary hyperreflective ovoid mass-like structures (PHOMS), peripapillary wrinkles (PPW) and retinal folds (RF) as potential biomarkers of elevated ICP. Methods: This single-center pilot study included subjects with untreated or incompletely treated high ICP. The retinas of these subjects were evaluated with averaged en-face optical coherence tomography (OCT), OCT retinal cross-sections (OCT B-scans), adaptive optics scanning light ophthalmoscopy (AOSLO), and fundus photos. Results: Seven subjects were included in the study. 6 subjects with high ICP (5 idiopathic intracranial hypertension, 1 medication induced, 30.8 ± 8.6 years, 75% female, 5 with papilledema) and 1 control (20-25 years) were included. PHOMS, PPW and RF were present in all subjects with papilledema, but neither in the high ICP subject without papilledema nor in the control subject. Averaged en-face OCT scans and AOSLO were more sensitive for PPW and RF than OCT B-scans and commercial fundus photos. Conclusion: PPW, RF and PHOMS volume have potential as non-invasive biomarkers of ICP. Novel imaging modalities may improve sensitivity. However, lack of automated image acquisition and processing limits current widespread adoption in clinical settings. Further research is needed to validate these structures as biomarkers for elevated ICP and improve clinical utility.

Rapid, Simple and Low-Cost Analytical Method Development for Quantification of Eltrombopag Olamine in Tablet Dosage by UV Spectroscopy Method.

BACKGROUND: Eltrombopag Olamine is a drug used to treat thrombocytopenia, a disorder where blood platelet counts get lower and severe aplastic anemia. It serves as a thrombopoietin receptor agonist, which give rise to platelet production in the bone marrow. OBJECTIVES: The objective of this study is to develop a simple, specific, accurate, precise and economical Ultraviolet spectroscopy method to estimate the amount of Eltrombopag Olamine in bulk and tablet dosage form. METHODS: The developed method was performed using methanol for identification and physicochemical characterization of the drug. The validation parameters like linearity, precision, accuracy, robustness limits of detection and quantitation, and specificity were assessed as per ICH Q2 (R2). RESULTS: The maximum absorbance wavelength (λmax) of the drug was found at 247 nm in methanol. The linearity was found in the concentration range of 2-14 µg/ml with regression equation y = 0.0619x - 0.0123 and r² = 0.999. The standard addition method was used to determine the accuracy of the developed method. The result was found in the % recovery range of 98-99%. The precision was done on λmax with respect to the parameters such as repeatability, intraday, and interday. The method was found to be precise as the % RSD value was found to be <2%. The detection limit value (LOD) and quantitation limit value (LOQ) were 0.0524 µg/ml and 0.1588 µg/ml, respectively. CONCLUSION: The developed method is simple, economical, accurate and selective. The developed method was adaptable for the estimation of Eltrombopag Olamine analysis in pharmaceutical dosage form and routine quality control laboratory.

Functional status of Indian children with juvenile idiopathic arthritis.

Background and Objectives: The functional disability status of Indian children with juvenile idiopathic arthritis is unidentified. In this cross-sectional study functional capacity of 60 juvenile idiopathic arthritis patients was assessed by the Childhood Health Assessment Questionnaire. Methods: A total of 60 juvenile idiopathic arthritis patients aged ranges from 1 to 12 years were recruited from a teaching hospital in eastern India. A childhood health assessment questionnaire was used to assess the functional health of children. Pain, patient's/parent's global assessment of general well-being, and physician's global assessment were assessed. Results: Childhood health assessment questionnaire disability index for oligoarticular juvenile idiopathic arthritis differed significantly from polyarticular juvenile idiopathic arthritis (P < 0.001), systemic-onset juvenile idiopathic arthritis (P = 0.018) and undifferentiated juvenile idiopathic arthritis (P < 0.001). There was a good to a strong positive correlation between the childhood health assessment questionnaire disability index with pain score, patient's/parent's global assessment score, and physician global assessment score for the total juvenile idiopathic arthritis cohort. regarding juvenile idiopathic arthritis subtypes, significant correlations were noted between the childhood health assessment questionnaire disability index with the patient's/parent's global assessment and physician's global assessment (except for enthesitis-related arthritis). Conclusions: Assessment and documentation of the functional health status of juvenile idiopathic arthritis patients will improve the management of the disease.

Suppression of OGN in lung myofibroblasts attenuates pulmonary fibrosis by inhibiting integrin αv-mediated TGF-ß/Smad pathway activation.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) represents a severe and progressive manifestation of idiopathic interstitial pneumonia marked by an uncertain etiology along with an unfavorable prognosis. Osteoglycin (OGN), belonging to the small leucine-rich proteoglycans family, assumes pivotal functions in both tissue formation and damage response. However, the roles and potential mechanisms of OGN in the context of lung fibrosis remain unexplored. METHODS: The assessment of OGN expression levels in fibrotic lungs was conducted across various experimental lung fibrosis mouse models. To elucidate the effects of OGN on the differentiation of lung myofibroblasts, both OGN knockdown and OGN overexpression were employed in vitro. The expression of integrin αv, along with its colocalization with lysosomes and latency-associated peptide (LAP), was monitored in OGN-knockdown lung myofibroblasts. Furthermore, the role of OGN in lung fibrosis was investigated through OGN knockdown utilizing adeno-related virus serotype 6 (AAV6)-mediated delivery. RESULTS: OGN exhibited upregulation in both lungs and myofibroblasts across diverse lung fibrosis mouse models. And laboratory experiments in vitro demonstrated that OGN knockdown inhibited the TGF-ß/Smad signaling pathway in lung myofibroblasts. Conversely, OGN overexpression promoted TGF-ß/Smad pathway in these cells. Mechanistic insights revealed that OGN knockdown facilitated lysosome-mediated degradation of integrin αv while inhibiting its binding to latency-associated peptide (LAP). Remarkably, AAV6-targeted OGN knockdown ameliorated the extent of lung fibrosis in experimental mouse models. CONCLUSION: Our results indicate that inhibiting OGN signaling could serve as a promising therapeutic way for lung fibrosis.

Clinical Impact of Telomere Length Testing for Interstitial Lung Disease.

BACKGROUND: Shortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown. RESEARCH QUESTION: What is the clinical impact of TL testing on the management of ILD? STUDY DESIGN AND METHODS: Patients were evaluated in the Columbia University ILD clinic and underwent CLIA-certified TL testing by flow cytometry and fluorescence in-situ hybridization (FlowFISH) as part of clinical management. Short TL was defined as below the 10th age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH. Patients were offered genetic counseling and testing if they had short TL or a family history of ILD. FlowFISH TL was compared against research qPCR TL measurement. RESULTS: A total of 108 patients underwent TL testing, including those with clinical features of short telomere syndrome such as familial pulmonary fibrosis (50%) or extrapulmonary manifestations in the patient (25%) or a relative (41%). The overall prevalence of short TL was 46% and was similar across clinical ILD diagnoses. The number of short telomere clinical features was independently associated with detecting short TL (OR 2.00, 95% CI [1.27, 3.32]). TL testing led to clinical management changes for 35 (32%) patients, most commonly resulting in reduction or avoidance of immunosuppression. Of the patients who underwent genetic testing (n=34), a positive or candidate diagnostic finding in telomere-related genes was identified in 10 (29%) patients. Inclusion of TL testing below the 1st percentile helped reclassify 8 of 9 variants of uncertain significance (VUS) into actionable findings. The qPCR test correlated with FlowFISH, but age-adjusted percentile cutoffs may not be equivalent between the two assays. INTERPRETATION: Incorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants.

N-Phenyl-2-Pyridone-Derived Endoperoxide Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis Progression by Three-Pronged Action.

We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone, thus targeting multiple mechanisms for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half-life of 8.3 hours without the generation of other by-products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of HIF-1α protein, but also inhibits the TGF-ß1 induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3-methyl-N-phenyl-2-pyridone, and triplet oxygen could downregulate HIF-1α and relieve tumor hypoxia which is a critical issue in conventional PDT. Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases.

Ventriculoperitoneal shunt patients and glaucoma: a cohort analysis of the NPH registry.

BACKGROUND: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a chronic condition affecting the elderly. It is characterized by a triad of symptoms and radiological findings. Glaucoma is the leading cause of irreversible blindness worldwide. Earlier studies have proposed that the rate of glaucoma is higher in iNPH patients, and of a possible link between ventriculoperitoneal shunt (VP) treatment and the development of glaucoma. OBJECTIVES: This study aimed to determine the prevalence of glaucoma among iNPH patients and assess the impact of VPs on glaucoma prevalence. METHODS: A cohort study was conducted at Kuopio University Hospital (KUH), including 262 patients with a ventriculoperitoneal shunt. Clinical data were obtained from the Kuopio NPH Registry and medical records. Patients were grouped by iNPH status: iNPH (+) - probable/possible iNPH (n = 192), and iNPH (-) - other causes of hydrocephalus (congenital, secondary, obstructive) (n = 70). We conducted statistical analysis using the Independent Samples T-test, Fisher's exact test, and Pearson Chi-Square. We compared demographics, glaucoma prevalence, brain biopsies positive for Amyloid-ß (Aß) and hyperphosphorylated tau (HPτ) as well as comorbidities for hypertension and diabetes medication. Age stratification assessed glaucoma prevalence in the full cohort. RESULTS: Both iNPH (+) and iNPH (-) groups had comparable demographic and comorbidity profiles. The prevalence of glaucoma in the iNPH (+) group was 11.5% (n = 22) and 11.4% (n = 8) in the iNPH (-) group without a statistically significant difference (p = 1.000). Brain biopsies positive for Amyloid-ß (Aß) and hyperphosphorylated tau (HPτ) were similar. CONCLUSIONS: Neither shunted iNPH patients nor those with a comorbid condition other than iNPH showed a markedly higher prevalence of glaucoma. Instead, both groups exhibited age-related increases in glaucoma prevalence, similar to the trends observed in population-based studies. Our data does not suggest a correlation between VP shunts and an elevated rate of glaucoma.

Ultrasonographic evaluation of changes in the joint before and after intra-articular injection in children with juvenile idiopathic arthritis.

OBJECTIVE: The aim of this study is to ultrasonographically (US) evaluate the course of the knee joint in oligoarticular juvenile idiopathic arthritis (JIA) patients who received intra-articular steroid (IAS) application to the knee joint. METHODS: 237 knee joints of 175 patients with oligoarticular JIA were evaluated retrospectively. The patients were divided into two groups: those who received only IAS therapy and those who were methotrexate to IAS therapy. Synovial fluid grade changes, synovial proliferation in B mode examination and power Doppler (PD) changes were evaluated with musculoskeletal ultrasonography (MSUS) separately for each joint before the treatment and at the 2nd, 6th and 12th weeks of the treatment. RESULTS: The percentages of regression in synovial fluid grade at the second, sixth, and 12th weeks were respectively 73.4%, 88.6%, and 89.0% (n=174, 210, 211, respectively). Meanwhile, the percentages of regression in PD grade were 69.2%, 82.7%, and 84.0% (n=164, 196, 199, respectively). At the second, sixth and 12th weeks, the percentage of those with synovial fluid grade 0 was 24.1%, 54.9%, 73.4%, respectively (n=57, 130, 174, respectively), while the percentage of those with PD grade 0 was 39.7%, 67.9%, 80.6%, respectively (n=94,161,191, respectively). The percentage of those without synovial proliferation in the second, sixth and 12th weeks was found to be 26.2%, 54.9%, 73.8% respectively (n=62, 130, 175, respectively). The mean time to regression of synovial fluid, synovial proliferation, and PD in the only IAS group was significantly short. The percentage of synovitis regression was higher in the only IAS group at all weeks. This difference was especially more pronounced in the early period. When the 12th-week results were evaluated, there was no difference between the two groups. CONCLUSION: This study highlights the utility of MSUS in evaluating the early results of IAS therapy applied to the knee joint in oligoarticular JIA patients.

18F-FDG accumulation at the early onset of acute exacerbation of idiopathic interstitial pneumonia on 18F-FDG PET/CT: A case report.

Acute exacerbation of idiopathic interstitial pneumonias (AE-IIPs) is a disease associated with a poor prognosis in patients with IIPs. However, the specific characteristics of fluorine-18 2-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging for AE-IIPs remain unclear. Herein, we present the case of a patient with lung cancer combined with IIPs who underwent 18F-FDG PET/CT at the early onset of AE-IIPs. The scan, conducted 18 days post-bronchoscopy for lung cancer evaluation, revealed AE-IIPs before the onset of respiratory failure. New ground-glass opacities appeared, accompanied by significant 18F-FDG accumulation extending beyond these regions. To the best of our knowledge, this report represents the first assessment of 18F-FDG PET/CT images at the early onset of AE-IIPs before respiratory failure in humans. The observed features in this PET image could potentially contribute to our understanding of the pathophysiology of AE-IIPs.

An Idiopathic Sterile Thyroid Abscess in a Five-Year-Old Child.

We would like to share a case study of a five-year-old child who complained of a painful mass on the front of his neck, with a fever of 98°F. Sometimes thyroid abscesses may be overlooked due to their rarity and are lower down on our list of differential diagnoses. Neck ultrasonography confirmed our findings. A thorough analysis of the literature showed that causal bacteria are required for almost all abscesses. However, in our instance, the aspirated fluid culture revealed no growth, indicating that the abscess was sterile. When patients present with severe neck swelling, this case report emphasizes the significance of considering thyroid abscess as one of the differential diagnoses since early detection is critical to minimize the risk of complications.

Parotid saliva and blood biomarkers in juvenile idiopathic arthritis in relation to temporomandibular joint magnetic resonance imaging findings.

BACKGROUND: Juvenile idiopathic arthritis (JIA) often affects the temporomandibular joint (TMJ) caused by an abnormal immune system that includes overactive inflammatory processes. Salivary biomarkers may be a powerful tool that can help establishing diagnosis, prognosis and monitor disease progress. OBJECTIVE: The objective was to investigate biomarkers in parotid saliva and blood plasma in relation to temporomandibular joint (TMJ) magnetic resonance imaging (MRI) findings in patients with JIA and healthy individuals. METHODS: Forty-five children aged 6 to 16 years with JIA and 16 healthy age- and sex-matched controls were included. Unstimulated parotid saliva samples and venous blood were collected. Biochemical analyses were performed for the cytokine biomarkers. The participants underwent MR imaging of the TMJs, where changes in the inflammatory and the damage domains were assessed. RESULTS: In the JIA patients, lower concentrations of IL-6R and gp130 were found in parotid saliva than in plasma. Higher concentrations of IL-6 were found in parotid saliva than in plasma. IL-6, IL-6R and gp130 in parotid saliva explained the presence of bone marrow oedema and effusion in the JIA patients. CONCLUSIONS: This study suggests that the IL-6 family in parotid saliva is associated with TMJ bone marrow oedema and effusion in patients with JIA, suggesting that IL-6 has promising properties as a parotid saliva biomarker for TMJ inflammatory activity.

Hypoxia Promotes Invadosome Formation by Lung Fibroblasts.

Lung parenchymal hypoxia has emerged as a cardinal feature of idiopathic pulmonary fibrosis (IPF). Hypoxia promotes cancer cell invasion and metastasis through signaling that is dependent upon the lysophosphatidic acid (LPA) receptor, LPA1 (LPAR1). Abundant data indicate that LPA1-dependent signaling also enhances lung fibrogenesis in IPF. We recently reported that fibroblasts isolated from the lungs of individuals with IPF have an increased capacity to form subcellular matrix-degradative structures known as invadosomes, an event that correlates with the degree of lung fibrosis. We therefore hypothesized that hypoxia promotes invadosome formation in lung fibroblasts through LPA1-dependent signaling. Here, it is demonstrated that invadosome formation by fibroblasts from the lungs of individuals with advanced IPF is inhibited by both the tyrosine receptor kinase inhibitor nintedanib and inhibition of LPA1. In addition, exposure of normal human lung fibroblasts to either hypoxia or LPA increased their ability to form invadosomes. Mechanistically, the hypoxia-induced invadosome formation by lung fibroblasts was found to involve LPA1 and PDGFR-Akt signaling. We concluded that hypoxia increases the formation of invadosomes in lung fibroblasts through the LPA1 and PDGFR-Akt signaling axis, which represents a potential target for suppressing lung fibrosis.

Fasting alleviates bleomycin-induced lung inflammation and fibrosis via decreased Tregs and monocytes.

PURPOSE: Idiopathic pulmonary fibrosis (IPF), a chronic and progressively worsening condition characterized by interstitial lung inflammation and fibrosis of unknown etiology, has a grim prognosis. The treatment options for IPF are limited and new therapeutic strategies are urgently needed. Dietary restriction can improve various inflammatory diseases, but its therapeutic effect on bleomycin (BLM)-induced pulmonary fibrosis mouse model remains unclear. This study aims to investigate whether intermittent fasting (IF) can alleviate BLM-induced pulmonary inflammation and fibrosis. METHODS: Pulmonary fibrosis mouse models were induced by BLM. The IF group underwent 24-h fasting cycles for one week prior and three weeks following BLM administration. Meanwhile, the ad libitum feeding group had unrestricted access to food throughout the experiment. The evaluation focused on lung pathology via histological staining, qPCR analysis of collagen markers, and immune cell profiling through flow cytometry. RESULTS: IF group significantly reduced inflammation and fibrosis in lung tissues of BLM-induced mice compared to ad libitum feeding group. qPCR results showed IF remarkably decreased the mRNA expression of Col 1a and Col 3a in the lungs of BLM-induced mouse models. IF also reduced the numbers of regulatory T cells (Tregs), T helper 17 (Th17) cells, monocytes, and monocyte-derived alveolar macrophages (MoAMs) in the lung tissues. CONCLUSIONS: IF may improve BLM-induced pulmonary fibrosis by decreasing numbers of immune cells including Treg cells, Th17 â€‹cells, monocytes, and MoAMs in the lungs. This study offers experimental validation for dietary intervention as a viable treatment modality in IPF management.

Occupational and environmental risk factors for idiopathic pulmonary fibrosis: A case-control study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown etiology. The aim of this study was to evaluate the environmental and occupational risk factors of IPF. METHODS: This hospital-based, case-control study included 206 patients with IPF selected from the Seoul National University Bundang Hospital Interstitial Lung Disease registry and 167 controls without lung disease. Data on occupation, lifestyle, transportation, and types of environmental and occupational dust exposure were obtained using a questionnaire. IPF diagnosis was confirmed based on the recent guidelines, and the possibility of hypersensitivity pneumonitis was excluded. Multiple logistic regression was performed to determine the risk factors for IPF. RESULTS: After adjusting for age and sex, ever-smokers (odds ratio [OR], 2.35; 95 % confidence interval [CI]: 1.51-3.68) and individuals who smoked more than 30 pack-years (OR, 2.79; 95%CI: 1.70-4.68) showed an increased risk for IPF. Any occupational dust exposure (adjusted OR, 2.08; 95%CI: 1.19-3.72), especially exposure to chemicals (adjusted OR, 3.52; 99%CI: 1.56-9.05), was associated with IPF after adjusting for age, sex, and smoking. CONCLUSIONS: Smoking and occupational dust exposure are associated with an increased risk for IPF. Both factors have dose and duration-dependent relationships with the risk for IPF.

The role of quercetin in ameliorating bleomycin-induced pulmonary fibrosis: insights into autophagy and the SIRT1/AMPK signaling pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway. METHODS: Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy. RESULTS: Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin. CONCLUSION: This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.

Biomarkers in idiopathic pulmonary fibrosis: Current insight and future direction.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a dismal prognosis. Early diagnosis, accurate prognosis, and personalized therapeutic interventions are essential for improving patient outcomes. Biomarkers, as measurable indicators of biological processes or disease states, hold significant promise in IPF management. In recent years, there has been a growing interest in identifying and validating biomarkers for IPF, encompassing various molecular, imaging, and clinical approaches. This review provides an in-depth examination of the current landscape of IPF biomarker research, highlighting their potential applications in disease diagnosis, prognosis, and treatment response. Additionally, the challenges and future perspectives of biomarker integration into clinical practice for precision medicine in IPF are discussed.

Clinical practice guidelines for the diagnosis and management of acute sensorineural hearing loss.

OBJECTIVE: Acute sensorineural hearing loss represents a spectrum of conditions characterized by sudden onset hearing loss. The "Clinical Practice Guidelines for the Diagnosis and Management of Acute Sensorineural Hearing Loss" were issued as the first clinical practice guidelines in Japan outlining the standard diagnosis and treatment. The purpose of this article is to strengthen the guidelines by adding the scientific evidence including a systematic review of the latest publications, and to widely introduce the current treatment options based on the scientific evidence. METHODS: The clinical practice guidelines were completed by 1) retrospective data analysis (using nationwide survey data), 2) systematic literature review, and 3) selected clinical questions (CQs). Additional systematic review of each disease was performed to strengthen the scientific evidence of the diagnosis and treatment in the guidelines. RESULTS: Based on the nationwide survey results and the systematic literature review summary, the standard diagnosis flowchart and treatment options, including the CQs and recommendations, were determined. CONCLUSION: The guidelines present a summary of the standard approaches for the diagnosis and treatment of acute sensorineural hearing loss. We hope that these guidelines will be used in medical practice and that they will initiate further research.

CSF formation rate-a potential glymphatic flow parameter in hydrocephalus?

BACKGROUND: Studies indicate that brain clearance via the glymphatic system is impaired in idiopathic normal pressure hydrocephalus (INPH). This has been suggested to result from reduced cerebrospinal fluid (CSF) turnover, which could be caused by a reduced CSF formation rate. The aim of this study was to determine the formation rate of CSF in a cohort of patients investigated for INPH and compare this to a historical control cohort. METHODS: CSF formation rate was estimated in 135 (75 ± 6 years old, 64/71 men/women) patients undergoing investigation for INPH. A semiautomatic CSF infusion investigation (via lumbar puncture) was performed. CSF formation rate was assessed by downregulating and steadily maintaining CSF pressure at a zero level. During the last 10 min, the required outflow to maintain zero pressure, i.e., CSF formation rate, was continuously measured. The values were compared to those of a historical reference cohort from a study by Ekstedt in 1978. RESULTS: Mean CSF formation rate was 0.45 ± 0.15 ml/min (N = 135), equivalent to 27 ± 9 ml/hour. There was no difference in the mean (p = 0.362) or variance (p = 0.498) of CSF formation rate between the subjects that were diagnosed as INPH (N = 86) and those who were not (N = 43). The CSF formation rate in INPH was statistically higher than in the reference cohort (0.46 ± 0.15 vs. 0.40 ± 0.08 ml/min, p = 0.005), but the small difference was probably not physiologically relevant. There was no correlation between CSF formation rate and baseline CSF pressure (r = 0.136, p = 0.115, N = 135) or age (-0.02, p = 0.803, N = 135). CONCLUSIONS: The average CSF formation rate in INPH was not decreased compared to the healthy reference cohort, which does not support reduced CSF turnover. This emphasizes the need to further investigate the source and routes of the flow in the glymphatic system and the cause of the suggested impaired glymphatic clearance in INPH.