Assessment of neurofluid dynamics in relation to clinical improvement after tap-test: pilot study.

PURPOSE: Idiopathic Normal pressure hydrocephalus (iNPH) is an under-diagnosed in elderly patients but none of the diagnostic tests are currently sufficiently sensitive or specific. The objective of this study was to analyze the dynamics of neurofluids by PC-MRI in relation to clinical evolution as measured using the iNPH grading scale after tap-test. METHOD: We prospectively included patients with suspected iNPH. All these patients underwent PCMRI to assess craniospinal hemohydrodynamics with analysis of the stroke volume of the cephalospinal fluid (CSF) within the Sylvius' aqueduct, within the high cervical subarachnoid spaces and the arteriovenous stroke volume. By this means, we calculated a compliance index. Morphological analysis was carried out using the DESH score. The infusion test was measuring the resistance to CSF flow. We analysed all these parameters according to the clinical improvement of the patients. RESULTS: 23 patients were included. Compliance index assessed by PC-MRI was significantly higher in the group of patients with improvement > 10% (p = 0.015). CONCLUSIONS: Our study highlights the importance of investigating arteriovenous and CSF interactions in iNPH. This involves understanding the physiological and pathophysiological mechanisms related to the circulation of neurofluids. The analysis of the interactions of these neurofluids allows for a comprehensive understanding of the system.

Construction and verification of risk predicting models to evaluate the possibility of hydrocephalus following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Hydrocephalus following a ruptured aneurysm portends a poor prognosis. The authors aimed to establish a nomogram to predict the risk of hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A total of 421 patients with aSAH who were diagnosed by digital subtraction angiography in The General Hospital of Northern Theater Command center from January 2020 to June 2021 were screened to establish the training cohort. An additional 135 patients who enrolled between July 2021 and May 2022 were used for the validation cohort. Variate difference analysis and stepwise logistic regression (model A) and univariate and multivariate logistic regressions (model B) were respectively used to construct two models. Then, the net reclassification improvement (NRI), integrated discrimination improvement (IDI), and receiver operating characteristic (ROC) curve were used to compare the predictive abilities of the two models. Finally, two nomograms were constructed and externally validated. RESULTS: After screening, 556 patients were included. The area under the ROC curve of models A and B in the training cohort were respectively 0.884 (95 % confidence interval [CI]: 0.847-0.921) and 0.834 (95 % CI: 0.787-0.881). The prediction ability of the model A was superior to model B (NRI > 0, IDI > 0, p < 0.05). The C-index of models A and B was 0.8835 and 0.8392, respectively. Regarding clinical usefulness, the two models offered a net benefit with a threshold probability of between 0.12 and 1 in the decision curve analysis, suggesting that the two models can accurately predict hydrocephalus events. CONCLUSIONS: Both models have good prediction accuracy. Compared with model B, model A has better discrimination and calibration. Further, the easy-to-use nomogram can help neurosurgeons to make rapid clinical decisions and apply early treatment measures in high-risk groups, which ultimately benefits patients.

Longstanding overt ventriculomegaly diagnosed in adolescents, not adults: a pediatric case report.

BACKGROUND: Longstanding overt ventriculomegaly in adults (LOVA) is a new form of progressive hydrocephalus characterized by onset in early childhood and gradual progression into adulthood. Patients with LOVA are usually asymptomatic in childhood. The diagnosis of LOVA in adolescence has not been reported. CASE REPORT: A patient with macrocephaly and mild ventriculomegaly from infancy developed headache exacerbation and cognitive dysfunction at the age of 11 years. Brain magnetic resonance imaging showed mild tri-ventriculomegaly with no radiological aggravation compared to imaging at the age of 8 years. No papilledema was observed. Drainage of 15 ml of spinal fluid via a lumbar puncture relieved the headache and cognitive dysfunction. Based on repeated improvements in cognitive function and headaches after spinal fluid drainage, we diagnosed the patient with LOVA with symptom onset in early adolescence. A ventriculoperitoneal shunt was placed, and the headaches disappeared completely. The full-scale intellectual quotient, verbal comprehension, and working memory improved significantly. CONCLUSIONS: LOVA may manifest as early as adolescence. The clinical presentation, age, clinical, radiological features, and management vary, and a spinal tap exam is useful for diagnosing LOVA, even in children. The spinal tap exam may be indicated in children with longstanding ventriculomegaly and deteriorating neurological symptoms to diagnose this "treatable intellectual disability."

The value of ventricular measurements in the prediction of shunt dependency after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Chronic hydrocephalus requiring shunt placement is a common complication of aneurysmal subarachnoid hemorrhage (SAH). Different risk factors and prediction scores for post-SAH shunt dependency have been evaluated so far. We analyzed the value of ventricle measurements for prediction of the need for shunt placement in SAH patients. METHODS: Eligible SAH cases treated between 01/2003 and 06/2016 were included. Initial computed tomography scans were reviewed to measure ventricle indices (bifrontal, bicaudate, Evans', ventricular, Huckman's, and third ventricle ratio). Previously introduced CHESS and SDASH scores for shunt dependency were calculated. Receiver operating characteristic analyses were performed for diagnostic accuracy of the ventricle indices and to identify the clinically relevant cut-offs. RESULTS: Shunt placement followed in 221 (36.5%) of 606 patients. In univariate analyses, all ventricular indices were associated with shunting (all: p<0.0001). The area under the curve (AUC) ranged between 0.622 and 0.662. In multivariate analyses, only Huckman's index was associated with shunt dependency (cut-off at ≥6.0cm, p<0.0001) independent of the CHESS score as baseline prediction model. A combined score (0-10 points) containing the CHESS score components (0-8 points) and Huckman's index (+2 points) showed better diagnostic accuracy (AUC=0.751) than the CHESS (AUC=0.713) and SDASH (AUC=0.693) scores and the highest overall model quality (0.71 vs. 0.65 and 0.67), respectively. CONCLUSIONS: Ventricle measurements are feasible for early prediction of shunt placement after SAH. The combined prediction model containing the CHESS score and Huckman's index showed remarkable diagnostic accuracy regarding identification of SAH individuals requiring shunt placement. External validation of the presented combined CHESS-Huckman score is mandatory.

How should we treat long-standing overt ventriculomegaly in adults (LOVA)? A retrospective cohort study.

Long-standing overt ventriculomegaly in adults (LOVA) is a heterogenous group of conditions with differing presentations. Few studies have evaluated success rates of available surgical treatments, or ascertained the natural history. There is a need to assess the efficacy of both endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) as first-line treatments. We conducted a retrospective, single-centre study of adults with LOVA at a tertiary neurosurgery centre in England, UK, aiming to identify presentation, management strategy, and outcome following treatment. A total of 127 patients were included (mean age 48.1 years, 61/127 male). Most patients were symptomatic (73.2%, n = 93/127, median symptom duration 10 months). The most common symptoms were gait ataxia, headache, and cognitive decline (52.8%, 50.4%, and 33.9%, respectively). Fourteen patients had papilloedema. Ninety-one patients (71.7%) underwent surgery (84 ETV, 7 VPS). Over a median follow-up of 33.0 months (interquartile range [IQR] 19.0-65.7), 82.4% had a clinical improvement after surgery, and 81.3% had radiological improvement. Clinical improvement rates were similar between ETV and VP shunt groups (82.1% vs 85.7%, p = 0.812). Surgical complication rates were significantly lower in the ETV group than the VP shunt group (4.8% vs 42.9%, p < 0.001). Of the patients treated surgically, 20 (22.0%) underwent further surgery, with 14 patients improving. This study demonstrates the efficacy of ETV as a first-line treatment for LOVA.

Longstanding overt ventriculomegaly in adults (LOVA) with patent aqueduct: surgical outcome and etiopathogenesis of a possibly distinct form of chronic hydrocephalus.

PURPOSE: Longstanding overt ventriculomegaly in adults (LOVA) represents a form of chronic adulthood hydrocephalus with symptomatic manifestation in late adulthood. Based on the patency of the aqueduct, two different subcohorts of LOVA can be distinguished. Surgical treatments of this condition are also debated. Therefore, we analyzed preoperative characteristics and clinical outcome after different surgical treatments in a subgroup of LOVA patients with a patent aqueduct. METHODS: Eighteen LOVA patients with a patent aqueduct consecutively treated at our institution between July 2013 and December 2019 were analyzed for this study. Median age was 70 years. Preoperative radiological and clinical features, surgical procedures (ventriculo-peritoneal shunt or endoscopic third ventriculostomy), and outcomes were collected. Successful outcome was qualitatively defined as an improvement or a halt of progression of the presenting symptoms at follow-up, and quantitatively by changes in mRS and iNPHGS scales. RESULTS: Twelve patients underwent an ETV as a primary treatment, while 6 underwent VPS. A total of 22.2% of them were lost to follow-up. Median follow-up time was 38 months. Six patients (66.7%) in the ETV cohort achieved a successful outcome after treatment, with a complication rate of 11.1%. Two patients underwent rescue VPS after ETV failure with a good outcome. Four patients (100%) underwent primary VPS and achieved a satisfactory outcome after treatment, with a reported complications rate of 25%. CONCLUSION: LOVA with patent aqueduct represents, in our opinion, a distinct clinical form of chronic hydrocephalus. For this subgroup, as well as for other forms of LOVA, ETV remains an acceptable first-line treatment option considering the good results, and the low complication rate, obtained in those patients and the hypothesis that hydrocephalus is due to an "intracisternal" obstruction.

Deficits of Learning and Spatial Memory are Associated with Increased Pyknosis of Pyramidal Neurons of the Hippocampus of Adult Rats with Chronic Hydrocephalus.

BACKGROUND: The hippocampus is the brain's centre for the consolidation of short-term and spatial memory that enables navigation. Hippocampal injury occurs in hydrocephalus and is associated with loss of memory. OBJECTIVE: We assessed pyknotic changes in kaolin-induced chronic hydrocephalus in adult rats using qualitative and quantitative means, and related these to memory deficits in the rats. METHODS: Adult rats were randomly divided into control and experimental groups. Hydrocephalus was induced by intracisternal injection of 0.1ml sterile kaolin suspension for 6weeks. Control rats received sham injections. Spatial memory was assessed with the Morris water maze test. Coronal sections of the brains were grouped into either mild or moderate hydrocephalus and then stained with H&E and cresyl violet stains. Thus, there were three groups: control, mild hydrocephalus and moderate hydrocephalus (n=10), respectively. RESULTS: Shrinking and thinning of the hippocampal tissue, distortion of the pyramidal layer and pyknotic cells were observed in the CA1 and CA3 regions of the hydrocephalic rats. The pyknotic indices in the mild hydrocephalic rat (Cornus Ammonis, CA) CA1, CA2, CA3 (54.30±1.38; 27.62±0.83; 57.61±0.74) and moderate hydrocephalic rat CA1, CA2, CA3 (48.18±0.67; 32.00±0.84; 42.41±1.19) regions were significantly increased compared to the controls' CA1, CA2, CA3 (12.14±0.56; 9.21±0.36; 13.04±0.59). CONCLUSION: Chronic hydrocephalus in adult rats was associated with cell death in all the regions of the hippocampus, irrespective of the degree of ventricular enlargement. The extent of cell death corresponded with the severity of learning and memory deficits. CONTEXTE: L'hippocampe est le centre du cerveau pour la consolidation de la mémoire à court terme et de la mémoire spatiale qui permet la navigation. Une lésion de l'hippocampe se produit dans l'hydrocéphalie et est associée à la perte de mémoire. OBJECTIF: Nous avons évalué les changements pyknotiques dans l'hydrocéphalie chronique induite par le kaolin chez des rats adultes en utilisant des moyens qualitatifs et quantitatifs, et nous les avons reliés aux déficits de mémoire chez les rats. MÉTHODES: Des rats adultes ont été répartis au hasard en groupes témoins et expérimentaux. L'hydrocéphalie a été induite par injection intracisternale de 0,1 ml de suspension stérile de kaolin pendant 6 semaines. Les rats témoins ont reçu des injections simulées. La mémoire spatiale a été évaluée par le test du labyrinthe aquatique de Morris. Les sections coronales des cerveaux ont été regroupées en hydrocéphalie légère ou modérée, puis colorées au H&E et au crésyl violet. Il y avait donc trois groupes : contrôle, hydrocéphalie légère et hydrocéphalie modérée (n=10), respectivement. RÉSULTATS: Un rétrécissement et un amincissement du tissu hippocampique, une distorsion de la couche pyramidale et des cellules pyknotiques ont été observés dans les régions CA1 et CA3 des rats hydrocéphales. Les indices pyknotiques dans les régions CA1, CA2 et CA3 des rats hydrocéphales légers (Cornus Ammonis, CA) (54,30±1,38 ; 27,62±0,83 ; 57,61±0,74) et des rats hydrocéphales modérés CA1, CA2 et CA3 (48. 18±0.67 ; 32.00±0.84 ; 42.41±1.19) ont été significativement augmentées par rapport aux régions CA1, CA2, CA3 des témoins (12.14±0.56 ; 9.21±0.36 ; 13.04±0.59). CONCLUSION: L'hydrocéphalie chronique chez les rats adultes était associée à la mort cellulaire dans toutes les régions de l'hippocampe, quel que soit le degré d'élargissement ventriculaire. L'étendue de la mort cellulaire correspondait à la sévérité des déficits d'apprentissage et de mémoire. MOTS CLÉS: Hydrocéphalie chronique, hippocampe, rats adultes, mémoire, cellules pyknotiques.

Protective Effects of Transforming Growth Factor-ß1 Knockdown in Human Umbilical Cord Mesenchymal Stem Cells against Subarachnoid Hemorrhage in a Rat Model.

BACKGROUND: Emerging evidence indicates a beneficial effect of mesenchymal stem cell (MSC) transplantation in subarachnoid hemorrhage (SAH). Chronic hydrocephalus is a common complication after SAH, which is associated with subarachnoid fibrosis promoted by transforming growth factor-ß1 (TGF-ß1). This study investigated the effect of human umbilical cord derived MSCs (hUC-MSCs) with TGF-ß1 knockdown on chronic hydrocephalus after SAH. METHODS: About 0.5 mL autologous blood was injected into the cerebellomedullaris cistern of 6-week SD rats to establish SAH model. hUC-MSCs or hUC-MSCs carrying TGF-ß1 knockdown (1 × 105 cells) were intraventricularly transplanted at 1 day before surgery and at P10. Neurological behavior score and water maze test were performed to assess neurological functions. Hydrocephalus was evaluated by Nissl staining. Concentrations of proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. The levels of TGF-ß1, p-Smad2/3, and Smad2/3 were measured using western blotting. RESULTS: Intraventricular hUC-MSCs transplantation significantly attenuated SAH-induced chronic hydrocephalus, upregulation of inflammatory cytokines, and behavioral impairment. Knockdown of TGF-ß1 in hUC-MSCs enhanced these effects. hUC-MSCs also reduced the upregulation of TGF-ß1 levels and Smad2/3 phosphorylation after SAH, and this effect was also enhanced by TGF-ß1 knockdown. CONCLUSION: Transplantation of hUC-MSCs exerts beneficial effect after SAH, possibly be through inhibiting TGF-ß1/Smad2/3 signaling pathway. Knockdown of TGF-ß1 in hUC-MSCs enhanced these effects.

Predictors of Ventriculoperitoneal shunting following Subarachnoid Hemorrhage treated with External Ventricular Drainage.

BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) is commonly associated with hydrocephalus due to subarachnoid hemorrhage blood products obstructing cerebrospinal fluid outflow. Hydrocephalus after aSAH is routinely managed with temporary external ventricular drainage (EVD) followed by standard EVD weaning protocols, which determine the need for ventriculoperitoneal shunting (VPS). We sought to investigate aSAH patients who initially passed EVD weaning trials and had EVD removal, but later presented with recurrent, delayed, symptomatic hydrocephalus requiring a VPS. METHODS: We conducted a retrospective review of all patients at our tertiary care medical center who presented with aSAH, requiring an EVD. We analyzed variables associated with ultimate VPS dependency during hospitalization. RESULTS: We reviewed 489 patients with aSAH over a 6-year period (2008-2014). One hundred and thirty-eight (28.2%) developed hydrocephalus requiring a temporary EVD. Forty-four (31.9%) of these patients died or had withdrawal of care during admission, and were excluded from final analysis. Of the remaining 94 patients, 29 (30.9%) failed their clamp trial and required VPS. Sixty-five (69.1%) patients passed their clamp trial and were discharged without a VPS. However, 10 (15.4%) of these patients developed delayed hydrocephalus after discharge and ultimately required VPS [mean (range) days after discharge, 97.2 (35-188)]. Compared to early VPS, the delayed VPS group had a higher incidence of symptomatic vasospasm (90.0% vs 51.7%; P = 0.03). When comparing patients discharged from the hospital without VPS, delayed VPS patients also had higher 6- and 12-month mortality (P = 0.02) and longer EVD clamp trials (P < 0.01) than patients who never required VPS but had an EVD during hospitalization. Delayed hydrocephalus occurred in only 7.8% of patients who passed the initial EVD clamp trial, compared to 14.3% who failed the initial trial and 80.0% who failed 2 or more trials. CONCLUSION: Patients who failed their initial or subsequent EVD clamp trials had a small, but increased risk of developing delayed hydrocephalus ultimately requiring VPS. Additionally, the majority of patients who presented with delayed hydrocephalus also suffered symptomatic vasospasm. These associations should be further explored and validated in a larger prospective study.

Is endoscopic third ventriculostomy safe and efficient in the treatment of obstructive chronic hydrocephalus in adults? A prospective clinical and MRI study.

BACKGROUND: In case of suspected normal pressure hydrocephalus, MRI is performed systematically and can sometimes highlight an obstruction of the flow pathways of the CSF (aqueductal stenosis or other downstream obstruction). It seems legitimate for these patients to ask the question of a treatment with endoscopic third ventriculostomy (ETV), even if the late decompensation of an obstruction may suggest an association with a CSF resorption disorder. The aim of this study was to evaluate clinical and radiological evolution after ETV in a group of elderly patients with an obstructive chronic hydrocephalus (OCH). METHODS: ETV was performed in 15 patients with OCH between 2012 and 2017. Morphometric (callosal angle, ventricular surface, third ventricular width, and Evans' index) and velocimetric parameters (stroke volume of the aqueductal (SVa) CSF) parameters were measured prior and after surgery with brain MRI. The clinical score (mini-mental status examination (MMSE) and the modified Larsson's score, evaluating walking, autonomy, and incontinence) were performed pre- and postoperatively. RESULTS: SVa was less than 15 µL/R-R in 12 out of the 15 patients; in the other three cases, the obstruction was located at a distance from the middle part of the aqueduct. Fourteen out of 15 patients were significantly improved: mean Larsson's score decreased from 3.8 to 0.6 (P ≤ 0.01) and mean MMSE increased from 25.7 to 28 (P = 0.084). Evans' index and ventricular area decreased postoperatively and the callosal angle increased (P ≤ 0.01). The mean follow-up lasted 17.9 months. No postoperative complications were observed. CONCLUSION: ETV seems to be a safe and efficient alternative to shunt for chronic hydrocephalus with obstruction; the clinical improvement is usual and ventricular size decreases slightly.

Validation of the modified Graeb score in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Intraventricular hemorrhage (IVH) in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is a known negative predictor. Scoring systems like Fisher, Le Roux, and original Graeb score (oGS) are established to quantify the volume of IVH. The aim of this study was to evaluate the validity of the recently introduced modified Graeb score (mGS) in patients with aSAH. METHODS: A retrospective analysis of the validity of the oGS and mGS in 257 aSAH patients was performed to assess and compare the predictive value of hospital mortality, development of CHC, and early functional outcome. RESULTS: In univariate analysis, an increase in either the oGS or mGS was associated with a higher risk for hospital mortality, development of CHC, and poor early functional outcome. The correlation of the oGS and mGS was excellent using Pearson's product-moment (r = 0.918; p < 0.001). The predictive value of the oGS was superior to the predictive value of the mGS using receiver operating characteristics and corresponding area under the curve value as there was no statistical significant differences between the scores. CONCLUSIONS: Our study confirms the validity of the recently introduced mGS to quantify the volume of IVH and extends its value in aSAH. However, the mGS offers no additional predictive value for hospital mortality, development of CHC, and poor early functional outcome in patients with aSAH patients compared to the less complex oGS.

Reduced GLP-1R availability in the caudate nucleus with Alzheimer's disease.

The glucagon-like peptide-1 receptor (GLP-1R) agonists reduce glycated hemoglobin in patients with type 2 diabetes. Mounting evidence indicates that the potential of GLP-1R agonists, mimicking a 30 amino acid ligand, GLP-1, extends to the treatment of neurodegenerative conditions, with a particular focus on Alzheimer's disease (AD). However, the mechanism that underlies regulation of GLP-1R availability in the brain with AD remains poorly understood. Here, using whole transcriptome RNA-Seq of the human postmortem caudate nucleus with AD and chronic hydrocephalus (CH) in the elderly, we found that GLP-1R and select mRNAs expressed in glucose dysmetabolism and dyslipidemia were significantly altered. Furthermore, we detected human RNA indicating a deficiency in doublecortin (DCX) levels and the presence of ferroptosis in the caudate nucleus impacted by AD. Using the genome data viewer, we assessed mutability of GLP-1R and 39 other genes by two factors associated with high mutation rates in chromosomes of four species. Surprisingly, we identified that nucleotide sizes of GLP-1R transcript exceptionally differed in all four species of humans, chimpanzees, rats, and mice by up to 6-fold. Taken together, the protein network database analysis suggests that reduced GLP-1R in the aged human brain is associated with glucose dysmetabolism, ferroptosis, and reduced DCX+ neurons, that may contribute to AD.

Cytotoxic Lesions of the Corpus Callosum Associated with Aneurysmal Subarachnoid Hemorrhage May Influence Shunt-Dependent Chronic Hydrocephalus.

BACKGROUND: Cytotoxic lesions of the corpus callosum (CLOCCs) are occasionally associated with aneurysmal subarachnoid hemorrhage (aSAH). The effects of aSAH on clinical outcomes in such cases are unclear. The present study aimed to investigate the frequency and characteristics of CLOCCs associated with aSAH to ascertain the predictors of shunt-dependent chronic hydrocephalus (SDCH) after aSAH. METHODS: We retrospectively investigated cases of aSAH treated by coil embolization. Patients were divided into those with and without CLOCCs. Between-group differences were evaluated, including clinical outcomes and the characteristics of both the patients and the aneurysms. Patients were divided into those with and without SDCH to identify predictive factors of SDCH after aSAH focusing on CLOCCs. RESULTS: This single-center study included 196 patients with aSAH. All patients received coil embolization between April 2013 and March 2020. CLOCCs were detected in 38 (19.4%) patients. In the group with CLOCCs, male sex, poor severity grade at onset, acute hydrocephalus, SDCH (all P < 0.01), and Fisher group 3 or 4 (P = 0.04) were significantly more common than in the group without CLOCCs. Diabetes and CLOCCs were significant predictors of SDCH after aSAH in multivariate analysis (diabetes: P < 0.01, odds ratio: 6.73, 95% confidence interval: 1.61-28.09; CLOCCs: P < 0.01, odds ratio: 6.86, 95% confidence interval: 2.87-16.38). CONCLUSIONS: CLOCCs and SDCH were common in patients with poor-grade aSAH, and CLOCCs were independent predictors of SDCH after aSAH. Meticulous follow-up is necessary to detect SDCH after aSAH, especially in patients with poor-grade aSAH and CLOCCs.

Classification of Chronic Hydrocephalus in Adults: A Systematic Review and Analysis.

BACKGROUND: Chronic hydrocephalus in adults (CHiA) includes all nonacute forms of hydrocephalus occurring in adulthood. It covers a spectrum of disorders. Some of these have relatively agreed on definitions, while others are less well characterized. The existing medical classification systems lack adequate structure and are neither clinically oriented nor easy to use, which severely hampers research and clinical care efforts. METHODS: A systematic literature review and data analysis were performed, focusing on the terms "adult hydrocephalus" and "classification," using the PubMed, Scopus, and Cochrane Library databases. Data on terminology, definitions, patient demographics, symptom duration, and clinical presentations were extracted, analyzed, and compiled. A Delphi process was followed to define CHiA disorders. RESULTS: A total of 33 studies collectively used 48 terms to define various CHiA disorders. Different terms were used to describe similar conditions. CHiA disorders were found to be clustered into 7 distinctive clinical entities based on the clinical characteristics. CONCLUSIONS: An evidence-based new clinical classification for CHiA is suggested. Our review identified gaps in knowledge and areas for further research.

A predictive model in patients with chronic hydrocephalus following aneurysmal subarachnoid hemorrhage: a retrospective cohort study.

Objective: Our aim was to develop a nomogram that integrates clinical and radiological data obtained from computed tomography (CT) scans, enabling the prediction of chronic hydrocephalus in patients with aneurysmal subarachnoid hemorrhage (aSAH). Method: A total of 318 patients diagnosed with subarachnoid hemorrhage (SAH) and admitted to the Department of Neurosurgery at the Affiliated People's Hospital of Jiangsu University between January 2020 and December 2022 were enrolled in our study. We collected clinical characteristics from the hospital's medical record system. To identify risk factors associated with chronic hydrocephalus, we conducted both univariate and LASSO regression models on these clinical characteristics and radiological features, accompanied with penalty parameter adjustments conducted through tenfold cross-validation. All features were then incorporated into multivariate logistic regression analyses. Based on these findings, we developed a clinical-radiological nomogram. To evaluate its discrimination performance, we conducted Receiver Operating Characteristic (ROC) curve analysis and calculated the Area Under the Curve (AUC). Additionally, we employed calibration curves, and utilized Brier scores as an indicator of concordance. Additionally, Decision Curve Analysis (DCA) was performed to determine the clinical utility of our models by estimating net benefits at various threshold probabilities for both training and testing groups. Results: The study included 181 patients, with a determined chronic hydrocephalus prevalence of 17.7%. Univariate logistic regression analysis identified 11 potential risk factors, while LASSO regression identified 7 significant risk factors associated with chronic hydrocephalus. Multivariate logistic regression analysis revealed three independent predictors for chronic hydrocephalus following aSAH: Periventricular white matter changes, External lumbar drainage, and Modified Fisher Grade. A nomogram incorporating these factors accurately predicted the risk of chronic hydrocephalus in both the training and testing cohorts. The AUC values were calculated as 0.810 and 0.811 for each cohort respectively, indicating good discriminative ability of the nomogram model. Calibration curves along with Hosmer-Lemeshow tests demonstrated excellent agreement between predicted probabilities and observed outcomes in both cohorts. Furthermore, Brier scores (0.127 for the training and 0.09 for testing groups) further validated the predictive performance of our nomogram model. The DCA confirmed that this nomogram provides superior net benefit across various risk thresholds when predicting chronic hydrocephalus. The decision curve demonstrated that when an individual's threshold probability ranged from 5 to 62%, this model is more effective in predicting the occurrence of chronic hydrocephalus after aSAH. Conclusion: A clinical-radiological nomogram was developed to combine clinical characteristics and radiological features from CT scans, aiming to enhance the accuracy of predicting chronic hydrocephalus in patients with aSAH. This innovative nomogram shows promising potential in assisting clinicians to create personalized and optimal treatment plans by providing precise predictions of chronic hydrocephalus among aSAH patients.

Lumboperitoneal shunt and ventriculoperitoneal shunt for chronic hydrocephalus after aneurysmal subarachnoid hemorrhage: a comparison.

Objective: Chronic hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) results in poor neurological outcomes and cognitive deficits. Currently, the main treatments for chronic hydrocephalus include ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS); however, the optimal treatment for chronic hydrocephalus after aSAH remains controversial. Method: The records of 82 patients were retrospectively analyzed, and the patients were divided into VPS and LPS groups based on surgical methods. The efficacy, shunt successful rate and complications were compared. The assessments of treatment efficacy included the Evans index score (EIS), Keifer's hydrocephalus score (KHS), Mini-Mental State Examination (MMSE) score and functional independence measure (FIM). Patients were followed up for three months to observe the postoperative curative effects and complications. Results: The rate of shunt obstruction was significantly higher in the LPS group than that in the VPS group (p < 0.05), and the shunt successful rate was significantly higher in the VPS group than that in the LPS group (p < 0.05). The total rate of complications was 24.4% for LPS and 39% for VPS. The improvements in EIS, KHS, MMSE, and FIM within each group after the shunt were significantly different compared to those before shunt (p < 0.05). Compared to those in the LPS group, the improvements in EIS, KHS, MMSE, and FIM were significantly different in the VPS group after shunt (p < 0.05). Conclusion: Compared with LPS, VPS in the treatment for chronic hydrocephalus after aSAH had greater therapeutic efficacy, as indicated by improved radiological outcomes, improved shunt successful rate, improved clinical outcomes, and improved quality of life. Therefore, we believe that VPS is the preferred treatment option for chronic hydrocephalus after aSAH, while LPS should only be used as an alternative to VPS.

CLR (C-Reactive Protein to Lymphocyte Ratio) Served as a Promising Predictive Biomarker for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage (aSAH): A Retrospective Cohort Study.

Background: Subarachnoid hemorrhage is a devastating disease. Even after state-of-the-art treatment patients suffer from complications, including cerebral vasospasm (CVS), delayed cerebral ischemia (DCI), and chronic hydrocephalus (CH) following aneurysmal subarachnoid hemorrhage (aSAH). The aim of our study is to identify the predictive value of the C-reactive protein to lymphocyte ratio (CLR) for neurological functional outcome and complications after aSAH. Methods: We retrospectively analyzed a total of 166 aSAH patients who met the inclusion criteria enrolled in our study. Multivariate logistic regression analyses were performed to evaluate the independent risk factors. The predictive value of different models was compared by calculating the areas under the receiver operating characteristic (ROC) curve. Results: On-admission levels of CLR in patients with poor outcomes (6 months mRS 3-6), CVS, DCI, and CH were significantly higher than those in patients with good outcomes (6 months mRS 0-2), non-CVS, non-DCI, and non-CH. Multivariate logistic regression analysis revealed that admission CLR was independently associated with CVS (OR [95% CI] 2.116 [1.507-2.971]; p < 0.001), and DCI (OR [95% CI] 1.594 [1.220-2.084]; p = 0.001). In ROC analysis, the area under the curve (AUC) of CLR for poor outcomes (6 months mRS 3-6), CVS, DCI, and CH prediction were (AUC [95% CI] 0.639 [0.555-0.724]; p = 0.002), (AUC [95% CI] 0.834 [0.767-0.901]; p < 0.001), (AUC [95% CI] 0.679 [0.581-0.777]; p < 0.001), and (AUC [95% CI] 0.628 [0.543-0.713]; p = 0.005) revealing that admission CLR had a favorable predictive value for CVS after aSAH. The sensitivity and specificity of admission CLR for CVS prediction were 77.1% and 75.4%. On-admission CLR of 0.757 mg × 10-6 was identified as the best cutoff threshold to discriminate between CVS and non-CVS (CVS: CLR < 0.757 mg × 10-6 11/100 [11.0%] vs. CLR ≥ 0.757 mg × 10-6 37/66 [56.1%]; p < 0.001). Conclusions: High levels of on-admission CLR serve as an independent risk factor for CVS and DCI after aSAH. Admission CLR is an easy-to-quantify laboratory parameter that efficiently predicts the CVS after aSAH, which can provide some guidance for clinicians to evaluate for possible progression and treatment strategies in patients with aSAH.

Automatic assessment of disproportionately enlarged subarachnoid-space hydrocephalus from 3D MRI using two deep learning models.

Background: Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key feature for Hakim disease (idiopathic normal pressure hydrocephalus: iNPH), but subjectively evaluated. To develop automatic quantitative assessment of DESH with automatic segmentation using combined deep learning models. Methods: This study included 180 participants (42 Hakim patients, 138 healthy volunteers; 78 males, 102 females). Overall, 159 three-dimensional (3D) T1-weighted and 180 T2-weighted MRIs were included. As a semantic segmentation, 3D MRIs were automatically segmented in the total ventricles, total subarachnoid space (SAS), high-convexity SAS, and Sylvian fissure and basal cistern on the 3D U-Net model. As an image classification, DESH, ventricular dilatation (VD), tightened sulci in the high convexities (THC), and Sylvian fissure dilatation (SFD) were automatically assessed on the multimodal convolutional neural network (CNN) model. For both deep learning models, 110 T1- and 130 T2-weighted MRIs were used for training, 30 T1- and 30 T2-weighted MRIs for internal validation, and the remaining 19 T1- and 20 T2-weighted MRIs for external validation. Dice score was calculated as (overlapping area) × 2/total area. Results: Automatic region extraction from 3D T1- and T2-weighted MRI was accurate for the total ventricles (mean Dice scores: 0.85 and 0.83), Sylvian fissure and basal cistern (0.70 and 0.69), and high-convexity SAS (0.68 and 0.60), respectively. Automatic determination of DESH, VD, THC, and SFD from the segmented regions on the multimodal CNN model was sufficiently reliable; all of the mean softmax probability scores were exceeded by 0.95. All of the areas under the receiver-operating characteristic curves of the DESH, Venthi, and Sylhi indexes calculated by the segmented regions for detecting DESH were exceeded by 0.97. Conclusion: Using 3D U-Net and a multimodal CNN, DESH was automatically detected with automatically segmented regions from 3D MRIs. Our developed diagnostic support tool can improve the precision of Hakim disease (iNPH) diagnosis.

Cerebrospinal Fluid Production and Absorption and Ventricular Enlargement Mechanisms in Hydrocephalus.

Cerebrospinal fluid (CSF) production and absorption concept significantly changed in the early 2010s from "third circulation theory" and "classical bulk flow theory" to a whole new one as follows: First, CSF is mainly produced from interstitial fluid excreted from the brain parenchyma, and CSF produced from the choroid plexus plays an important role in maintaining brain homeostasis. Second, CSF is not absorbed in the venous sinus via the arachnoid granules, but mainly in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways at the borders attached to the choroid plexus, e.g., the inferior choroidal point of the choroidal fissure, other than the foramina of Luschka and Magendie. In idiopathic normal pressure hydrocephalus (iNPH), the lateral ventricles and basal cistern are enlarged simultaneously due to the compensatory direct CSF pathways. The average total intracranial CSF volume increased from about 150 mL at 20 years to about 350 mL at 70 years due to the decrease in brain volume with aging and further increased above 400 mL in patients with iNPH. CSF movements are composed of a steady microflow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and dynamic pulsatile flow produced by the brain and cerebral artery pulsation, respiration, and head movement. Pulsatile CSF movements might totally decrease with aging, but it in the ventricles might increase at the foramina of Magendie and Luschka dilation. Aging CSF dynamics are strongly associated with ventricular dilatation in iNPH.

Preventive effect of intermittent cerebrospinal fluid drainage for secondary chronic hydrocephalus after aneurysmal subarachnoid hemorrhage.

BACKGROUND: The efficacy of intermittent cerebrospinal fluid (CSF) drainage compared with that of continuous CSF drainage in patients with subarachnoid hemorrhage (SAH) remains undetermined to date. Therefore, we investigated whether intermittent CSF drainage is effective in reducing secondary chronic hydrocephalus (sCH) after aneurysmal SAH. METHODS: Overall, 204 patients (69 men and 135 women) treated for aneurysmal SAH between 2007 and 2022 were included in this study. Following SAH onset, 136 patients were managed with continuous CSF drainage, whereas 68 were managed with intermittent CSF drainage. Logistic regression analyses were used to calculate the age-adjusted and multivariate odds ratios for the development of sCH. The Cox proportional hazards regression model were used to compare the effects of intermittent and continuous CSF drainage on sCH development. RESULTS: Overall, 96 patients developed sCH among the 204 patients with SAH. In total, 74 (54.4%) of the 136 patients managed with continuous CSF drainage developed sCH, whereas 22 (32.4%) of the 68 patients managed with intermittent CSF drainage developed sCH. This demonstrated that the rate of sCH development was significantly lower among patients managed with intermittent CSF drainage. Compared with continuous CSF drainage, intermittent CSF drainage exhibited a multivariate odds ratio (95% confidential interval) of 0.25 (0.11-0.57) for sCH development. Intermittent CSF drainage was more effective (0.20, 0.04-0.95) in patients with severe-grade SAH than in those with mild-grade SAH (0.33, 0.12-0.95). Intermittent CSF drainage was ineffective in patients with acute hydrocephalus (8.37, 0.56-125.2), but it was effective in patients without acute hydrocephalus (0.11, 0.04-0.31). CONCLUSIONS: Compared with continuous CSF drainage, intermittent drainage is more effective in reducing sCH after aneurysmal SAH. Although intermittent drainage was ineffective in cases of co-occurrence of acute hydrocephalus, it was effective in reducing sCH development regardless of the severity of initial symptoms at SAH onset.