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1.
Sci Rep ; 14(1): 12966, 2024 06 05.
Article En | MEDLINE | ID: mdl-38839864

The inflow of CSF into perivascular spaces (PVS) in the brain is crucial for clearing waste molecules. Inefficiency in PVS flow leads to neurodegeneration. Failure of PVS flushing is associated with CSF flow impairment in the intracranial hydrodynamic condition of CSF hypo-pulsatility. However, enlarged PVS (ePVS), a finding indicative of PVS flow dysfunction, is also present in patients with derangement of CSF dynamics characterized by CSF hyper-pulsatility, which increases CSF flow. Intriguingly, two opposite intracranial hydrodynamic conditions would lead to the same result of impairing the PVS flushing. To investigate this issue, we assessed the subsistence of a dysfunctional interplay between CSF and PVS flows and, if the case, the mechanisms preventing a hyper-pulsatile brain from providing an effective PVS flushing. We analyzed the association between phase contrast MRI aqueductal CSF stroke volume (aqSV), a proxy of CSF pulsatility, and the burden of ePVS in chronic adult hydrocephalus, a disease involving a broad spectrum of intracranial hydrodynamics disturbances. In the 147 (85 males, 62 females) patients, the age at diagnosis ranged between 28 and 88 years (median 73 years). Ninety-seven patients had tri-ventriculomegaly and 50 tetra-ventriculomegaly. According to the extent of ePVS, 113 patients had a high ePVS burden, while 34 had a low ePVS burden. aqSV, which ranged between 0 and 562 µL (median 86 µL), was increased with respect to healthy subjects. Patients presenting with less ePVS burden had higher aqSV (p < 0.002, corrected for the multiple comparisons) than those with higher ePVS burden. The present study confirmed the association between CSF dynamics and PVS flow disturbances and demonstrated this association in intracranial hyper-pulsatility. Further studies should investigate the association between PVS flow failure and CSF hypo- and hyper-pulsatility as responsible/co-responsible for glymphatic failure in other neurodegenerative diseases, particularly in diseases in which CSF disturbances can be corrected, as in chronic adult hydrocephalus.


Glymphatic System , Hydrocephalus , Magnetic Resonance Imaging , Humans , Hydrocephalus/cerebrospinal fluid , Hydrocephalus/physiopathology , Hydrocephalus/pathology , Male , Female , Aged , Middle Aged , Adult , Glymphatic System/physiopathology , Glymphatic System/pathology , Aged, 80 and over , Cerebrospinal Fluid , Hydrodynamics , Stroke Volume , Cerebral Aqueduct/pathology , Cerebral Aqueduct/physiopathology , Chronic Disease
2.
Sultan Qaboos Univ Med J ; 24(2): 288-292, 2024 May.
Article En | MEDLINE | ID: mdl-38828259

Persistent hydrocephalus is common in children after resection of posterior fossa tumours. However, occurrence of subdural hygroma is very rare. We report the case of a 14-month-old child who presented at a paediatric neurology clinic in Muscat, Oman in 2021 who developed a tense subdural hygroma with stable hydrocephalus, in the early postoperative period, following posterior fossa tumour resection. We describe the distinctive clinical, radiological and pathological features associated with the development of a tense subdural hygroma. We also discuss the management by cerebrospinal fluid diversion, which includes either a ventriculoperitoneal or subduroperitoneal shunt. This unique condition is distinguished from external hydrocephalus by features that are critical to the management strategy.


Infratentorial Neoplasms , Subdural Effusion , Humans , Infratentorial Neoplasms/surgery , Subdural Effusion/etiology , Infant , Oman , Male , Hydrocephalus/etiology , Hydrocephalus/surgery , Postoperative Complications/etiology , Postoperative Complications/diagnosis , Ventriculoperitoneal Shunt/adverse effects , Ventriculoperitoneal Shunt/methods , Female
3.
Neurosurg Rev ; 47(1): 201, 2024 May 02.
Article En | MEDLINE | ID: mdl-38695962

Optimizing the treatment of hydrocephalus remains a major challenge in adult and pediatric neurosurgery. Currently, clinical treatment relies heavily on anatomic imaging of ventricular size and clinical presentation. The emergence of functional and structural brain connectivity imaging has provided the basis for a new paradigm in the management of hydrocephalus. Here we review the pertinent advances in this field. Following PRISMA-ScR guidelines for scoping reviews, we searched PubMed for relevant literature from 1994 to April 2023 using hydrocephalus and MRI-related terms. Included articles reported original MRI data on human subjects with hydrocephalus, while excluding non-English or pre-1994 publications that didn't match the study framework. The review identified 44 studies that investigated functional and/or structural connectivity using various MRI techniques across different hydrocephalus populations. While there is significant heterogeneity in imaging technology and connectivity analysis, there is broad consensus in the literature that 1) hydrocephalus is associated with disruption of functional and structural connectivity, 2) this disruption in cerebral connectivity can be further associated with neurologic compromise 3) timely treatment of hydrocephalus restores both cerebral connectivity and neurologic compromise. The robustness and consistency of these findings vary as a function of patient age, hydrocephalus etiology, and the connectivity region of interest studied. Functional and structural brain connectivity imaging shows potential as an imaging biomarker that may facilitate optimization of hydrocephalus treatment. Future research should focus on standardizing regions of interest as well as identifying connectivity analysis most pertinent to clinical outcome.


Hydrocephalus , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/pathology
4.
J Clin Neurosci ; 125: 168-174, 2024 Jul.
Article En | MEDLINE | ID: mdl-38820856

BACKGROUND: Ventriculoperitoneal (VP) shunt insertion is a means of diverting cerebrospinal fluid (CSF) for management of hydrocephalus. Revision rates, operating time, and length of stay (LOS) following laparoscopic insertion of the distal catheter have been mixed. There are limited data on the role of adhesiolysis during VP shunt insertion. Valve characteristics have also been shown to influence patient outcomes. There is a paucity of Australian data reporting on the effect of these variables on shunt outcomes. We aimed to study patient demographics, indications, and surgical and instrument variables in the Australian context. METHODS: We performed a retrospective, multi-surgeon, single-centre analysis of VP shunts inserted in adults via an open or laparoscopic technique. Data on patient demographics and surgery characteristics were collected from the hospital medical records and the Australasian Shunt Registry. The primary outcome was shunt revision rate and secondary outcomes were postoperative complications, operating time and LOS, and shunt survivability. RESULTS: Fifty-six participants were eligible for analysis. The overall revision rate was 14.3 %, which was lower than the national average. The distal catheter revision rate was 0 %. Laparoscopic insertion of the distal catheter was shown to significantly reduce operating time (70.4 min in the open group and 50.7 min in the laparoscopic group, p < 0.001). This was demonstrated across different aetiologies, and when controlling for age and valve-type (p < 0.05). The revision rate of non-programmable was higher than programmable valves (42.9 % versus 2.9 %, respectively). There were no differences between previous abdominal surgery, LOS, complication, or revision rate between open and laparoscopic insertion. VP shunt survivability was greater in the laparoscopic group (90-day shunt survival of 96.7 % and 92 % in the laparoscopy and open groups, respectively; p > 0.05). We did not find any significant difference in operating time or length of stay for age, sex, or previous abdominal surgery, even when accounting for surgical technique. Indication and shunt survivability varied widely between age groups. The use of laparoscopic insertion increased over time, though surgeons did not crossover techniques. CONCLUSIONS: The overall distal revision rate of VP shunts is low. Laparoscopic insertion of the distal catheter reduces operating time and may improve shunt survivability. Larger studies are needed to confirm differences in shunt survivability in open versus laparoscopic distal catheter insertion, between age groups, clinical indications, and valve type on patient outcomes.


Hydrocephalus , Laparoscopy , Ventriculoperitoneal Shunt , Humans , Ventriculoperitoneal Shunt/methods , Ventriculoperitoneal Shunt/adverse effects , Retrospective Studies , Male , Female , Middle Aged , Australia , Hydrocephalus/surgery , Aged , Adult , Laparoscopy/methods , Reoperation/statistics & numerical data , Length of Stay/statistics & numerical data , Treatment Outcome , Postoperative Complications/epidemiology , Aged, 80 and over , Young Adult , Operative Time
5.
Neurosciences (Riyadh) ; 29(2): 122-127, 2024 May.
Article En | MEDLINE | ID: mdl-38740404

OBJECTIVES: To calculate The Evans Index (EI) in normal Individuals. Ventricular enlargement is referred to as hydrocephalus. Computer tomography (CT) scans are commonly used to investigate such intracranial pathologies. The EI is an important parameter for diagnosing hydrocephalus. METHODS: We included all patients who underwent Computer tomography (CT) scan of the brain that was reported as normal. The mean EI was calculated for the whole sample stratified by age, gender, and ethnicity. Patients with an initial report indicating any intracranial pathology, such as hydrocephalus, tumors, hemorrhages, or neurodegenerative disorders, were excluded. RESULTS: A total of 1,330 brain CT scans carried out at our institution were reviewed retrospectively from August 2021 to December 2021. A total of 423 CT scans were screened after excluding 25 patients with abnormal imaging findings and 14 repeated images for the same patients. A total of 384 patients were included. The mean EI for the entire sample was 0.2550±0.0277. There was a minimal but statistically significant difference based on gender, with a mean EI of 0.2588±0.0274 for males and 0.2517±0.0276 for females (p=0.012). There was no statistically significant difference between Saudi and non-Saudi patients. EI increased progressively with age in both genders. CONCLUSION: Our EI values were similar to many of those reported in other countries, which supports the use of the 0.3 cutoff for the diagnosis of hydrocephalus, regardless of gender, age, or ethnicity.


Hydrocephalus , Tomography, X-Ray Computed , Humans , Male , Female , Saudi Arabia , Middle Aged , Adult , Hydrocephalus/diagnostic imaging , Aged , Retrospective Studies , Adolescent , Young Adult , Child , Aged, 80 and over , Child, Preschool
7.
BMC Pediatr ; 24(1): 350, 2024 May 22.
Article En | MEDLINE | ID: mdl-38773409

BACKGROUND: Neural tube defects (NTDs) account for the largest proportion of congenital anomalies of the central nervous system and result from failure of the neural tube to close spontaneously between the 3rd and 4th weeks of in utero development. Prognosis and treatment outcome depends on the nature and the pattern of the defect. The nature of treatment outcomes and its pattern associated with grave prognosis is not well known in the study area. OBJECTIVE: The aim of study was to determine the patterns and short term neurosurgical management outcomes of newborns with neural tube defects admitted at Felege Hiwot Specialized Hospital. METHODS: Institutional based retrospective cross-sectional study among neonates, who were admitted at Felege Hiwot Specialized Hospital with neural tube defects from January 1st to December, 30th, 2018 was conducted. All Charts of Neonates with confirmed diagnosis of neural tube defects were included as part of the study. Trained data collectors (medical interns) supervised by trained supervisors (general practitioners) collected the data using a pretested data extraction format. Data were coded, entered and analyzed using SPSS version 23 software. Frequency and cross tabulations were used to summarize descriptive statistics of data, and tables and graphs were used for data presentation. RESULT: About 109 patients had complete documentation and imaging confirmed neural tube defects. Myelomeningocele was the commonest pattern 70 (64.2%). Thoracolumbar spine was the commonest site of presentation 49(45%). The most common associated impairment was hydrocephalus 37(33.9%). Forty-five (41.1%) had multiple complications. The mortality rate was 7.3%, 44% were discharged with sequalae and 36.7% were discharged without impairment. The significant causes of death were infection 66.7% and Chiari crisis 33.3%. CONCLUSION: Myelomeningocele was the most frequent clinical pattern of neural tube defect and thoracolumbar spine was the commonest site. Isolated neural tube defect was the commonest finding. There were multiple complications after surgery accompanied with meningitis and hydrocephalus. The mortality rate among neonates with neural tube defects was considerably high. The commonest causes of death were infection and Chiari crisis.


Neural Tube Defects , Humans , Infant, Newborn , Cross-Sectional Studies , Retrospective Studies , Ethiopia/epidemiology , Neural Tube Defects/surgery , Female , Male , Neurosurgical Procedures/statistics & numerical data , Neurosurgical Procedures/methods , Treatment Outcome , Hydrocephalus/surgery , Hospitals, Special/statistics & numerical data , Meningomyelocele/surgery , Meningomyelocele/complications
8.
Curr Oncol ; 31(5): 2410-2419, 2024 04 24.
Article En | MEDLINE | ID: mdl-38785461

Therapeutic management of patients with leptomeningeal carcinomatosis (LC) may require treatment of concomitant hydrocephalus (HC) in addition to intrathecal chemotherapy (ITC). Ventriculoperitoneal shunts (VPS) equipped with a valve for manual deactivation of shunt function and a concomitant reservoir for application of ITC pose an elegant solution to both problems. The present study evaluates indication, feasibility, and safety of such a modified shunt/reservoir design (mS/R). All patients with LC aged ≥ 18 years who had undergone mS/R implantation between 2013 and 2020 at the authors' institution were further analyzed. ITC was indicated following the recommendation of the neuro-oncological tumor board and performed according to a standardized protocol. Sixteen patients with LC underwent mS/R implantation for subsequent ITC and concomitant treatment of HC. Regarding HC-related clinical symptoms, 69% of patients preoperatively exhibited lethargy, 38% cognitive impairment, and 38% (additional) visual disturbances. Postoperatively, 86% of patients achieved subjective improvement of HC-related symptoms. Overall, postoperative complications occurred in three patients (19%). No patient encountered cancer treatment-related complications. The present study describes a combination procedure consisting of a standard VPS-system and a standard reservoir for patients suffering from LC and HC. No cancer treatment-related complications occurred, indicating straightforward handling and thus safety.


Hydrocephalus , Injections, Spinal , Meningeal Carcinomatosis , Ventriculoperitoneal Shunt , Humans , Ventriculoperitoneal Shunt/methods , Meningeal Carcinomatosis/drug therapy , Female , Male , Middle Aged , Hydrocephalus/surgery , Adult , Aged , Feasibility Studies
9.
Tomography ; 10(5): 654-659, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38787010

This brief report aimed to show the utility of photon-counting technology alongside standard cranial imaging protocols for visualizing shunt valves in a patient's cranial computed tomography scan. Photon-counting CT scans with cranial protocols were retrospectively surveyed and four types of shunt valves were encountered: proGAV 2.0®, M.blue®, Codman Certas®, and proSA®. These scans were compared with those obtained from non-photon-counting scanners at different time points for the same patients. The analysis of these findings demonstrated the usefulness of photon-counting technology for the clear and precise visualization of shunt valves without any additional radiation or special reconstruction patterns. The enhanced utility of photon-counting is highlighted by providing superior spatial resolution compared to other CT detectors. This technology facilitates a more accurate characterization of shunt valves and may support the detection of subtle abnormalities and a precise assessment of shunt valves.


Photons , Tomography, X-Ray Computed , Humans , Tomography, X-Ray Computed/methods , Retrospective Studies , Cerebrospinal Fluid Shunts/instrumentation , Cerebrospinal Fluid Shunts/methods , Male , Female , Hydrocephalus/diagnostic imaging , Skull/diagnostic imaging , Aged
10.
Adv Tech Stand Neurosurg ; 49: 123-138, 2024.
Article En | MEDLINE | ID: mdl-38700683

Intraventricular tumors of the lateral and third ventricles are relatively rare, accounting for 1-2% of all primary brain tumors in most large series [1-4]. They can be uniquely challenging to approach due to their deep location, propensity to become large before they are discovered, and association with hydrocephalus [5, 6]. The surgeon's goal is to develop a route to these deep lesions that will cause the least morbidity, provide adequate working space, and achieve a complete resection. This must be performed with minimal manipulation of the neural structures encircling the ventricles, avoiding functional cortical areas, and acquiring early control of feeding vessels [7, 8].


Cerebral Ventricle Neoplasms , Humans , Cerebral Ventricle Neoplasms/surgery , Cerebral Ventricle Neoplasms/pathology , Cerebral Ventricles/surgery , Corpus Callosum/surgery , Hydrocephalus/surgery , Lateral Ventricles/surgery , Neurosurgical Procedures/methods
11.
Cell Biochem Funct ; 42(4): e4034, 2024 06.
Article En | MEDLINE | ID: mdl-38715189

L1 syndrome, a neurological disorder with an X-linked inheritance pattern, mainly results from mutations occurring in the L1 cell adhesion molecule (L1CAM) gene. The L1CAM molecule, belonging to the immunoglobulin (Ig) superfamily of neurocyte adhesion molecules, plays a pivotal role in facilitating intercellular signal transmission across membranes and is indispensable for proper neuronal development and function. This study identified a rare missense variant (c.1759G>C; p.G587R) in the L1CAM gene within a male fetus presenting with hydrocephalus. Due to a lack of functional analysis, the significance of the L1CAM mutation c.1759G>C (p.G587R) remains unknown. We aimed to perform further verification for its pathogenicity. Blood samples were obtained from the proband and his parents for trio clinical exome sequencing and mutation analysis. Expression level analysis was conducted using western blot techniques. Immunofluorescence was employed to investigate L1CAM subcellular localization, while cell aggregation and cell scratch assays were utilized to assess protein function. The study showed that the mutation (c.1759G>C; p.G587R) affected posttranslational glycosylation modification and induced alterations in the subcellular localization of L1-G587R in the cells. It resulted in the diminished expression of L1CAM on the cell surface and accumulation in the endoplasmic reticulum. The p.G587R altered the function of L1CAM protein and reduced homophilic adhesion capacity of proteins, leading to impaired adhesion and migration of proteins between cells. Our findings provide first biological evidence for the association between the missense mutation (c.1759G>c; p.G587R) in the L1CAM gene and L1 syndrome, confirming the pathogenicity of this missense mutation.


Mutation, Missense , Neural Cell Adhesion Molecule L1 , Humans , Male , HEK293 Cells , Hydrocephalus/genetics , Hydrocephalus/metabolism , Hydrocephalus/pathology , Neural Cell Adhesion Molecule L1/genetics , Neural Cell Adhesion Molecule L1/metabolism , Pedigree , Infant, Newborn
12.
J Med Invest ; 71(1.2): 154-157, 2024.
Article En | MEDLINE | ID: mdl-38735712

BACKGROUND: Adjustable shunt valves that have been developed for managing hydrocephalus rely on intrinsically magnetic components ; thus, artifacts with these valves on magnetic resonance imaging (MRI) are inevitable. No studies on valve-induced artifacts in lumboperitoneal shunt (LPS) surgery have been published. Therefore, this study aimed to evaluate valve-induced artifacts in LPS. METHODS: We retrospectively reviewed all MRIs obtained between January 2023 and June 2023 in patients with an implanted Codman CERTAS Plus adjustable shunt valve (Integra Life Sciences, Princeton, New Jersey, USA). The valve was placed <1 cm subcutaneously on the paravertebral spinal muscle of the back, with its long axis perpendicular to the body axis. The scans were performed using a Toshiba Medical Systems 1.5 Tesla scanner. The in-plane artifact sizes were assessed as the maximum distance of the artifact from the expected region of the back. RESULTS: All spinal structures or spinal cords can be recognized, even with valve-induced artifacts. The median maximum valve-induced artifact distance on T1-weighted axial imaging was 25.63 mm (mean, 25.98 mm ; range, 22.24-30.94 mm). The median maximum valve-induced artifact distance on T2-weighted axial imaging was 25.56 mm (mean, 26.27 mm ; range, 21.83-29.53 mm). CONCLUSION: LPS surgery with adjustable valve implantation on paravertebral muscles did not cause valve-induced artifacts in the spine and spinal cord. We considered that LPS could simplify the postoperative care of these patients. J. Med. Invest. 71 : 154-157, February, 2024.


Artifacts , Magnetic Resonance Imaging , Humans , Retrospective Studies , Magnetic Resonance Imaging/methods , Male , Female , Middle Aged , Aged , Adult , Cerebrospinal Fluid Shunts/methods , Aged, 80 and over , Hydrocephalus/surgery , Hydrocephalus/diagnostic imaging , Paraspinal Muscles/diagnostic imaging
13.
Fluids Barriers CNS ; 21(1): 47, 2024 May 30.
Article En | MEDLINE | ID: mdl-38816737

BACKGROUND: Bidirectional reciprocal motion of cerebrospinal fluid (CSF) was quantified using four-dimensional (4D) flow magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) MRI. To estimate various CSF motions in the entire intracranial region, we attempted to integrate the flow parameters calculated using the two MRI sequences. To elucidate how CSF dynamics deteriorate in Hakim's disease, an age-dependent chronic hydrocephalus, flow parameters were estimated from the two MRI sequences to assess CSF motion in the entire intracranial region. METHODS: This study included 127 healthy volunteers aged ≥ 20 years and 44 patients with Hakim's disease. On 4D flow MRI for measuring CSF motion, velocity encoding was set at 5 cm/s. For the IVIM MRI analysis, the diffusion-weighted sequence was set at six b-values (i.e., 0, 50, 100, 250, 500, and 1000 s/mm2), and the biexponential IVIM fitting method was adapted. The relationships between the fraction of incoherent perfusion (f) on IVIM MRI and 4D flow MRI parameters including velocity amplitude (VA), absolute maximum velocity, stroke volume, net flow volume, and reverse flow rate were comprehensively evaluated in seven locations in the ventricles and subarachnoid spaces. Furthermore, we developed a new parameter for fluid oscillation, the Fluid Oscillation Index (FOI), by integrating these two measurements. In addition, we investigated the relationship between the measurements and indices specific to Hakim's disease and the FOIs in the entire intracranial space. RESULTS: The VA on 4D flow MRI was significantly associated with the mean f-values on IVIM MRI. Therefore, we estimated VA that could not be directly measured on 4D flow MRI from the mean f-values on IVIM MRI in the intracranial CSF space, using the following formula; e0.2(f-85) + 0.25. To quantify fluid oscillation using one integrated parameter with weighting, FOI was calculated as VA × 10 + f × 0.02. In addition, the FOIs at the left foramen of Luschka had the strongest correlations with the Evans index (Pearson's correlation coefficient: 0.78). The other indices related with Hakim's disease were significantly associated with the FOIs at the cerebral aqueduct and bilateral foramina of Luschka. FOI at the cerebral aqueduct was also elevated in healthy controls aged ≥ 60 years. CONCLUSIONS: We estimated pulsatile CSF movements in the entire intracranial CSF space in healthy individuals and patients with Hakim's disease using FOI integrating VA from 4D flow MRI and f-values from IVIM MRI. FOI is useful for quantifying the CSF oscillation.


Cerebrospinal Fluid , Magnetic Resonance Imaging , Humans , Cerebrospinal Fluid/diagnostic imaging , Cerebrospinal Fluid/physiology , Adult , Male , Female , Magnetic Resonance Imaging/methods , Middle Aged , Young Adult , Aged , Hydrodynamics , Hydrocephalus/diagnostic imaging , Hydrocephalus/physiopathology , Hydrocephalus/cerebrospinal fluid , Brain/diagnostic imaging , Brain/physiology
14.
Nat Rev Dis Primers ; 10(1): 35, 2024 May 16.
Article En | MEDLINE | ID: mdl-38755194

Hydrocephalus is classically considered as a failure of cerebrospinal fluid (CSF) homeostasis that results in the active expansion of the cerebral ventricles. Infants with hydrocephalus can present with progressive increases in head circumference whereas older children often present with signs and symptoms of elevated intracranial pressure. Congenital hydrocephalus is present at or near birth and some cases have been linked to gene mutations that disrupt brain morphogenesis and alter the biomechanics of the CSF-brain interface. Acquired hydrocephalus can develop at any time after birth, is often caused by central nervous system infection or haemorrhage and has been associated with blockage of CSF pathways and inflammation-dependent dysregulation of CSF secretion and clearance. Treatments for hydrocephalus mainly include surgical CSF shunting or endoscopic third ventriculostomy with or without choroid plexus cauterization. In utero treatment of fetal hydrocephalus is possible via surgical closure of associated neural tube defects. Long-term outcomes for children with hydrocephalus vary widely and depend on intrinsic (genetic) and extrinsic factors. Advances in genomics, brain imaging and other technologies are beginning to refine the definition of hydrocephalus, increase precision of prognostication and identify nonsurgical treatment strategies.


Hydrocephalus , Humans , Hydrocephalus/physiopathology , Hydrocephalus/diagnosis , Hydrocephalus/therapy , Hydrocephalus/etiology , Hydrocephalus/complications , Child , Infant , Ventriculostomy/methods , Cerebrospinal Fluid Shunts/methods , Infant, Newborn
15.
PLoS Biol ; 22(5): e3002596, 2024 May.
Article En | MEDLINE | ID: mdl-38718086

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.


Autism Spectrum Disorder , Cilia , Ependyma , Mice, Knockout , Phenotype , Animals , Male , Mice , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/metabolism , Autism Spectrum Disorder/physiopathology , Behavior, Animal , Cilia/metabolism , Disease Models, Animal , Ependyma/metabolism , Hippocampus/metabolism , Hydrocephalus/genetics , Hydrocephalus/metabolism , Hydrocephalus/pathology , Hydrocephalus/physiopathology , Katanin/metabolism , Katanin/genetics , Mice, Inbred C57BL , Neurons/metabolism , Synapses/metabolism , Transcriptome/genetics
16.
BMC Pediatr ; 24(1): 325, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734598

BACKGROUND: Cerebrospinal fluid (CSF) shunts allow children with hydrocephalus to survive and avoid brain injury (J Neurosurg 107:345-57, 2007; Childs Nerv Syst 12:192-9, 1996). The Hydrocephalus Clinical Research Network implemented non-randomized quality improvement protocols that were shown to decrease infection rates compared to pre-operative prophylactic intravenous antibiotics alone (standard care): initially with intrathecal (IT) antibiotics between 2007-2009 (J Neurosurg Pediatr 8:22-9, 2011), followed by antibiotic impregnated catheters (AIC) in 2012-2013 (J Neurosurg Pediatr 17:391-6, 2016). No large scale studies have compared infection prevention between the techniques in children. Our objectives were to compare the risk of infection following the use of IT antibiotics, AIC, and standard care during low-risk CSF shunt surgery (i.e., initial CSF shunt placement and revisions) in children. METHODS: A retrospective observational cohort study at 6 tertiary care children's hospitals was conducted using Pediatric Health Information System + (PHIS +) data augmented with manual chart review. The study population included children ≤ 18 years who underwent initial shunt placement between 01/2007 and 12/2012. Infection and subsequent CSF shunt surgery data were collected through 12/2015. Propensity score adjustment for regression analysis was developed based on site, procedure type, and year; surgeon was treated as a random effect. RESULTS: A total of 1723 children underwent initial shunt placement between 2007-2012, with 1371 subsequent shunt revisions and 138 shunt infections. Propensity adjusted regression demonstrated no statistically significant difference in odds of shunt infection between IT antibiotics (OR 1.22, 95% CI 0.82-1.81, p = 0.3) and AICs (OR 0.91, 95% CI 0.56-1.49, p = 0.7) compared to standard care. CONCLUSION: In a large, observational multicenter cohort, IT antibiotics and AICs do not confer a statistically significant risk reduction compared to standard care for pediatric patients undergoing low-risk (i.e., initial or revision) shunt surgeries.


Anti-Bacterial Agents , Antibiotic Prophylaxis , Cerebrospinal Fluid Shunts , Humans , Cerebrospinal Fluid Shunts/adverse effects , Anti-Bacterial Agents/administration & dosage , Retrospective Studies , Child , Male , Child, Preschool , Female , Infant , Antibiotic Prophylaxis/methods , Adolescent , Injections, Spinal , Hydrocephalus/surgery , Catheters, Indwelling/adverse effects , Surgical Wound Infection/prevention & control , Catheter-Related Infections/prevention & control , Catheters
17.
Acta Neurochir (Wien) ; 166(1): 236, 2024 May 28.
Article En | MEDLINE | ID: mdl-38805061

BACKGROUND: Pineal region lesions in children are heterogenous pathologies often symptomatic due to occlusive hydrocephalus and thus elevated intracranial pressure (ICP). MRI-derived parameters to assess hydrocephalus are the optic nerve sheath diameter (ONSD) as a surrogate for ICP and the frontal occipital horn ratio (FOHR), representing ventricle volume. As elevated ICP may not always be associated with clinical signs, the adjunct of ONSD could help decision making in patients undergoing treatment. The goal of this study is to assess the available magnetic resonance imaging (MRI) of patients with pineal region lesions undergoing surgical treatment with respect to pre- and postoperative ONSD and FOHR as an indicator for hydrocephalus. METHODS: Retrospective data analysis was performed in all patients operated for pineal region lesions at a tertiary care center between 2010 and 2023. Only patients with pre- and postoperative MRI were selected for inclusion. Clinical data and ONSD at multiple time points, as well as FOHR were analyzed. Imaging parameter changes were correlated with clinical signs of hydrocephalus before and after surgical treatment. RESULTS: Thirty-three patients with forty operative cases met the inclusion criteria. Age at diagnosis was 10.9 ± 4.6 years (1-17 years). Hydrocephalus was seen in 80% of operative cases preoperatively (n = 32/40). Presence of hydrocephalus was associated with significantly elevated preoperative ONSD (p = 0.006). There was a significant decrease in ONSD immediately (p < 0.001) and at 3 months (p < 0.001) postoperatively. FOHR showed a slightly less pronounced decrease (immediately p = 0.006, 3 months p = 0.003). In patients without hydrocephalus, no significant changes in ONSD were observed (p = 0.369). In 6/6 patients with clinical hydrocephalus treatment failure, ONSD increased, but in 3/6 ONSD was the only discernible MRI change with unchanged FOHR. CONCLUSIONS: ONSD measurements may have utility in evaluating intracranial hypertension due to hydrocephalus in patients with pineal region tumors. ONSD changes appear to have value in assessing hydrocephalus treatment failure.


Hydrocephalus , Magnetic Resonance Imaging , Optic Nerve , Humans , Hydrocephalus/surgery , Hydrocephalus/diagnostic imaging , Hydrocephalus/etiology , Child , Male , Adolescent , Female , Retrospective Studies , Child, Preschool , Optic Nerve/diagnostic imaging , Optic Nerve/pathology , Optic Nerve/surgery , Infant , Magnetic Resonance Imaging/methods , Pineal Gland/surgery , Pineal Gland/diagnostic imaging , Pineal Gland/pathology , Treatment Outcome , Treatment Failure , Brain Neoplasms/surgery , Brain Neoplasms/complications , Brain Neoplasms/diagnostic imaging , Intracranial Hypertension/surgery , Intracranial Hypertension/diagnostic imaging , Intracranial Hypertension/etiology , Pinealoma/surgery , Pinealoma/complications , Pinealoma/diagnostic imaging
18.
Neurosurg Clin N Am ; 35(3): 379-387, 2024 Jul.
Article En | MEDLINE | ID: mdl-38782531

Cerebrospinal fluid (CSF) bathing the central nervous system is produced by brain and choroid plexus within the ventricles for re-absorption into the venous circulation through arachnoid granulations (AG). Communicating hydrocephalus results from disruption of the absorptive process, necessitating surgical catheter-based shunt placement to relieve excess pressure from CSF buildup. Adjustable valve designs and antibiotic impregnation have minimally impacted persistent failure rates and postoperative complications. To confront this challenge, we have developed an innovative endovascular shunt implant biologically inspired from AG function to restore the natural dynamics of CSF drainage while concurrently addressing the predominant factors contributing to conventional shunt malfunction.


Cerebrospinal Fluid Shunts , Hydrocephalus , Humans , Cerebrospinal Fluid Shunts/adverse effects , Cerebrospinal Fluid Shunts/methods , Cerebrospinal Fluid Shunts/instrumentation , Endovascular Procedures/methods , Endovascular Procedures/instrumentation , Hydrocephalus/surgery
19.
Nat Neurosci ; 27(6): 1103-1115, 2024 Jun.
Article En | MEDLINE | ID: mdl-38741020

The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. Here, to explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3 and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely, thymosin beta 4, thymosin beta 10 and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.


Brain , Subcommissural Organ , Animals , Mice , Brain/metabolism , Brain/growth & development , Brain/embryology , Subcommissural Organ/metabolism , Gene Expression Regulation, Developmental , Thymosin/metabolism , Thymosin/genetics , Mice, Transgenic , Hydrocephalus/genetics , Hydrocephalus/metabolism , Hydrocephalus/pathology , Neurons/metabolism , Cell Movement/physiology , Peptides/metabolism , Mice, Inbred C57BL
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