Unveiling the domino effect: a nine-year follow-up on pentalogy of central nervous system induced by a large unruptured cerebral arteriovenous malformation: a case report and literature review.

Background: The disruption of intracranial fluid dynamics due to large unruptured cerebral arteriovenous malformation (AVM) commonly triggers a domino effect within the central nervous system. This phenomenon is frequently overlooked in prior clinic and may lead to catastrophic misdiagnoses. Our team has documented the world's first case of so-called AVM Pentalogy (AVMP) induced by a AVM. Clinical presentation and result: A 30-year-old female was first seen 9 years ago with an occasional fainting, at which time a huge unruptured AVM was discovered. Subsequently, due to progressive symptoms, she sought consultations from several prestigious neurosurgical departments in China, where all consulting neurosurgeons opted for conservation treatment due to perceived surgical risks. During the follow-up period, the patient gradually presented with hydrocephalus, empty sella, secondary Chiari malformation, syringomyelia, and scoliosis (we called as AVMP). When treated in our department, she already displayed numerous symptoms, including severe intracranial hypertension. Our team deduced that the hydrocephalus was the primary driver of her AVMP symptoms, representing the most favorable risk profile for intervention. As expected, a ventriculoperitoneal shunt successfully mitigated all symptoms of AVMP at 21-months post-surgical review. Conclusion: During the monitoring of unruptured AVM, it is crucial to remain vigilant for the development or progression of AVMP. When any component of AVMP is identified, thorough etiological studies and analysis of cascade reactions are imperative to avert misdiagnosis. When direct AVM intervention is not viable, strategically addressing hydrocephalus as part of the AVMP may serve as the critical therapeutic focus.

Ventriculoperitoneal shunting obstruction: a multicentre clinical audit for cerebrospinal fluid parameters and its prediction role.

BACKGROUND: Shunt obstruction is a type of ventriculoperitoneal shunt (VPS) failure. Whether changes in cerebrospinal fluid (CSF) parameters can influence shunt outcomes or not is debatable. METHODS: In this study, we retrospectively included adult hydrocephalus patients who received VPS from 6 general hospitals in different provinces of China from November 2013 to September 2021. The inclusion criteria: Patients with hydrocephalus of all etiologies underwent shunt surgery from 6 general hospitals in different provinces of China were included in the study. The exclusion criteria: 1.Patients under the age of 18; 2.Patients who had previous shunt surgery; 3. Shunt failure from other factors; 4.Patients died from other causes; 5. Patients with incomplete data. The CSF of shunt patients had been analyzed at the time of shunt insertion. The CSF samples were collected and analyzed when the shunt was implanted. The relationship between CSF parameters and the incidence rate of shunt obstruction in one year was analyzed. RESULTS: A total of 717 eligible patients from 6 hospitals were included, of whom 59(8.23%) experienced obstruction. Multivariate logistic regression analysis identified that protein level(odds ratio [OR] 1.161, 95% CI 1.005 ~ 1.341, p = 0.043), decreased glucose level(< 2.5 mmol/L)(odds ratio 3.784, 95% confidence interval 1.872 ~ 7.652, p = 0.001) and protein level increase(> 0.45 g/L) (odds ratio 3.653, 95% confidence interval 1.931 ~ 6.910, p = 0.001)were independent risk factors of shunt obstruction. CONCLUSION: This study suggested that increased protein level (> 0.45 g/L) and decreased glucose level (< 2.5 mmol/L) in CSF indicated an increased risk of shunt obstruction in a patient with hydrocephalus. Thus, shunt surgery should be more carefully considered when the CSF glucose and protein were abnormal.

Research process, recap, and prediction of Chiari malformation based on bicentennial history of nomenclature and terms misuse.

There is an absent systematic analysis or review that has been conducted to clarify the topic of nomenclature history and terms misuse about Chiari malformations (CMs). We reviewed all reports on terms coined for CMs for rational use and provided their etymology and future development. All literature on the nomenclature of CMs was retrieved and extracted into core terms. Subsequently, keyword analysis, preceding and predicting (2023-2025) compound annual growth rate (CAGR) of each core term, was calculated using a mathematical formula and autoregressive integrated moving average model in Python. Totally 64,527 CM term usage was identified. Of these, 57 original terms were collected and then extracted into 24 core-terms. Seventeen terms have their own featured author keywords, while seven terms are homologous. The preceding CAGR of 24 terms showed significant growth in use for 18 terms, while 13, three, three, and five terms may show sustained growth, remain stable, decline, and rare in usage, respectively, in the future. Previously, owing to intricate nomenclature, Chiari terms were frequently misused, and numerous seemingly novel but worthless even improper terms have emerged. For a very basic neuropathological phenomenon tonsillar herniation by multiple etiology, a mechanism-based nosology seems to be more conducive to future communication than an umbrella eponym. However, a good nomenclature also should encapsulate all characteristics of this condition, but this is lacking in current CM research, as the pathophysiological mechanisms are not elucidated for the majority of CMs.

Prevalence and treatment of typical and atypical headaches in patients with Chiari I malformation: A meta-analysis and literature review.

OBJECTIVE: A meta-analysis was conducted to analyze the incidence of typical and atypical headaches and outcomes following various treatments in patients with Chiari I malformation. BACKGROUND: Headache is the most common symptom of Chiari malformation, which can be divided into typical and atypical subgroups to facilitate management. Much controversy surrounds the etiology, prevalence and optimal therapeutic approach for both types of headaches. METHOD: We identified relevant studies published before 30 July 2022, with an electronic search of numerous literature databases. The results of this study were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULT: A total of 1913 Chiari malformation type I CIM patients were identified, 78% of whom presented with headache, within this group cephalgia was typical in 48% and atypical in 29% of patients, and migraine was the most common type of atypical headache. The ratio of typical/atypical headaches with international classification of headache disorders diagnosis was 1.53, and without international classification of headache disorders diagnosis was 1.56, respectively. The pooled improvement rates of typical headaches following conservative treatment, extradural decompression and intradural decompression were 69%, 88%, and 92%, respectively. The corresponding improvement rates for atypical headaches were 70%, 57.47%, and 69%, respectively. The complication rate in extradural decompression group was significantly lower than in intradural decompression group (RR, 0.31; 95% CI: 0.06-1.59, I2 = 50%, P = 0.14). Low reoperation rates were observed for refractory headaches in extradural decompression and intradural decompression groups (1%). CONCLUSION: The International Classification of Headache Disorders can assist in screening atypical headaches. extradural decompression is preferred for typical headaches, while conservative therapy is optimal for atypical headaches. A definite correlation exists between atypical headaches and Chiari Malformation Type I patients with higher prevalence than in the general population. Importantly, decompression is effective in relieving headaches in this particular patient population.

Development of a novel glycolysis-related genes signature for isocitrate dehydrogenase 1-associated glioblastoma multiforme.

Background: The significant difference in prognosis between IDH1 wild-type and IDH1 mutant glioblastoma multiforme (GBM) may be attributed to their metabolic discrepancies. Hence, we try to construct a prognostic signature based on glycolysis-related genes (GRGs) for IDH1-associated GBM and further investigate its relationships with immunity. Methods: Differentially expressed GRGs between IDH1 wild-type and IDH1 mutant GBM were screened based on the TCGA database and the Molecular Signature Database (MSigDB). Consensus Cluster Plus analysis and KEGG pathway analyses were used to establish a new GRGs set. WGCNA, univariate Cox, and LASSO regression analyses were then performed to construct the prognostic signature. Then, we evaluated association of the prognostic signature with patients' survival, clinical characteristics, tumor immunogenicity, immune infiltration, and validated one hub gene. Results: 956 differentially expressed genes (DEGs) between IDH1 wild-type and mutant GBM were screened out and six key prognostically related GRGs were rigorously selected to construct a prognostic signature. Further evaluation and validation showed that the signature independently predicted GBM patients' prognosis with moderate accuracy. In addition, the prognostic signature was also significantly correlated with clinical traits (sex and MGMT promoter status), tumor immunogenicity (mRNAsi, EREG-mRNAsi and HRD-TAI), and immune infiltration (stemness index, immune cells infiltration, immune score, and gene mutation). Among six key prognostically related GRGs, CLEC5A was selected and validated to potentially play oncogenic roles in GBM. Conclusion: Construction of GRGs prognostic signature and identification of close correlation between the signature and immune landscape would suggest its potential applicability in immunotherapy of GBM in the future.

Microsurgical management of midbrain cavernous malformations: does lesion depth influence the outcome?

BACKGROUND: The purpose of this study was to clarify whether the intrinsic depth of midbrain cavernous malformations (MCMs) influenced the surgical outcome. METHODS: The authors conducted a retrospective study of 76 consecutive patients who underwent microsurgical resection of a MCM. The vascular lesions were categorized into 4 distinct groups based on how these lesions had altered the brainstem surface. Additionally, it was verified whether the actual aspect of the brainstem surface could be predicted only by evaluating the pertinent preoperative MRI slices. Clinical outcome was assessed by determining the modified Rankin Scale Score (mRS) before and after surgery. RESULTS: Twenty-three MCMs (30.3%) were located deeply within the midbrain. The overlying midbrain surface appeared to be normal (group nl). In 33 patients (43.4%), the midbrain surface showed only a yellowish discoloration (group yw). In another 14 individuals (18.4%), the midbrain surface was distorted by the underlying MCM and bulging out while the vascular lesion still remained covered by a thin parenchymal layer (group bg). In the smallest group comprising 6 patients (7.9%), the exophytic MCM had disrupted the midbrain surface and was clearly visible at microsurgical exposure (group ex). The mean mRS decreased in the group nl from 1.43 preoperatively to 0.61 at follow-up. CONCLUSION: This study demonstrates in a large patient population that a deep intrinsic MCM location is not necessarily associated with an unfavorable clinical outcome after microsurgical lesionectomy. Predicting the aspect of the midbrain surface by evaluating preoperative MR images alone was not sufficiently reliable.

Optimal access route for pontine cavernous malformation resection with preservation of abducens and facial nerve function.

OBJECTIVE: The aim of this study was to analyze the differences between posterolateral and posteromedial approaches to pontine cavernous malformations (PCMs) in order to verify the hypothesis that a posterolateral approach is more favorable with regard to preservation of abducens and facial nerve function. METHODS: The authors conducted a retrospective analysis of 135 consecutive patients who underwent microsurgical resection of a PCM. The vascular lesions were first classified in a blinded fashion into 4 categories according to the possible or only reasonable surgical access route. In a second step, the lesions were assessed according to which approach was performed and different patient groups and subgroups were determined. In a third step, the modified Rankin Scale score and the rates of permanent postoperative abducens and facial nerve palsies were assessed. RESULTS: The largest group in this series comprised 77 patients. Their pontine lesion was eligible for resection from either a posterolateral or posteromedial approach, in contrast to the remaining 3 patient groups in which the lesion location already had dictated a specific surgical approach. Fifty-four of these 77 individuals underwent surgery via a posterolateral approach and 23 via a posteromedial approach. When comparing these 2 patient subgroups, there was a statistically significant difference between postoperative rates of permanent abducens (3.7% vs 21.7%) and facial (1.9% vs 21.7%) nerve palsies. In the entire patient population, the abducens and facial nerve deficit rates were 5.9% and 5.2%, respectively, and the modified Rankin Scale score significantly decreased from 1.6 ± 1.1 preoperatively to 1.0 ± 1.1 at follow-up. CONCLUSIONS: The authors' results suggest favoring a posterolateral over a posteromedial access route to PCMs in patients in whom a lesion is encountered that can be removed via either surgical approach. In the present series, the authors have found such a constellation in 57% of all patients. This retrospective analysis confirms their hypothesis in a large patient cohort. Additionally, the authors demonstrated that 4 types of PCMs can be distinguished by preoperatively evaluating whether only one reasonable or two alternative surgical approaches are available to access a specific lesion. The rates of postoperative sixth and seventh nerve palsies in this series are substantially lower than those in the majority of other published reports.

Transcriptome-wide Profiling of Cerebral Cavernous Malformations Patients Reveal Important Long noncoding RNA molecular signatures.

Cerebral cavernous malformations (CCMs) are low-flow vascular malformations in the brain associated with recurrent hemorrhage and seizures. The current treatment of CCMs relies solely on surgical intervention. Henceforth, alternative non-invasive therapies are urgently needed to help prevent subsequent hemorrhagic episodes. Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism. Despite accumulating evidence demonstrating the role of lncRNAs in cerebrovascular disorders, their identification in CCMs pathology remains unknown. The objective of the current study was to identify lncRNAs associated with CCMs pathogenesis using patient cohorts having 10 CCM patients and 4 controls from brain. Executing next generation sequencing, we performed whole transcriptome sequencing (RNA-seq) analysis and identified 1,967 lncRNAs and 4,928 protein coding genes (PCGs) to be differentially expressed in CCMs patients. Among these, we selected top 6 differentially expressed lncRNAs each having significant correlative expression with more than 100 differentially expressed PCGs. The differential expression status of the top lncRNAs, SMIM25 and LBX2-AS1 in CCMs was further confirmed by qRT-PCR analysis. Additionally, gene set enrichment analysis of correlated PCGs revealed critical pathways related to vascular signaling and important biological processes relevant to CCMs pathophysiology. Here, by transcriptome-wide approach we demonstrate that lncRNAs are prevalent in CCMs disease and are likely to play critical roles in regulating important signaling pathways involved in the disease progression. We believe, that detailed future investigations on this set of identified lncRNAs can provide useful insights into the biology and, ultimately, contribute in preventing this debilitating disease.

Expression of HGF, MMP-9 and TGF-ß1 in the CSF and cerebral tissue of adult rats with hydrocephalus.

OBJECT: The hepatocyte growth factor (HGF), matrix metallopeptidase-9 (MMP-9) and transforming growth factor-ß1 (TGF-ß1) are important cytokines with modulatory actions in the nervous system. In this study, we attempted to investigate the role and expression of HGF, MMP-9 and TGF-ß1 in the cerebral tissue and cerebrospinal fluid (CSF) of adult rats with hydrocephalus induced via intraventricular kaolin injection. METHODS: Adult male Sprague-Dawley rats were randomly divided into two groups: control group (n = 12) and experimental group (n = 20). Kaolin was injected into the lateral ventricle of experimental animals. Control rats underwent the same procedure but received sterile saline injection instead of kaolin. Magnetic resonance imaging was used to assess ventricle size. The CSF was studied by enzyme-linked immunosorbent assay and the excised brains were studied by reverse-transcription polymerase chain reaction and immunohistochemical analyses to measure the messenger RNA and protein expression level of HGF, MMP-9 and TGF-ß1. RESULTS: Hydrocephalus was induced in all the rats after kaolin injection into the lateral ventricle. After 2 weeks, the expressions of HGF, MMP-9 and TGF-ß1 in the CSF and cerebral tissue were significantly increased in the experimental group compared with the control group. CONCLUSIONS: This results indicated that HGF, MMP-9 and TGF-ß1 may participate in the formation and prognosis of hydrocephalus after kaolin induction.

Minocycline reduces reactive gliosis in the rat model of hydrocephalus.

BACKGROUND: Reactive gliosis had been implicated in injury and recovery patterns associated with hydrocephalus. Our aim is to determine the efficacy of minocycline, an antibiotic known for its anti-inflammatory properties, to reduce reactive gliosis and inhibit the development of hydrocephalus. RESULTS: The ventricular dilatation were evaluated by MRI at 1-week post drugs treated, while GFAP and Iba-1were detected by RT-PCR, Immunohistochemistry and Western blot. The expression of GFAP and Iba-1 was significantly higher in hydrocephalic group compared with saline control group (p < 0.05). Minocycline treatment of hydrocephalic animals reduced the expression of GFAP and Iba-1 significantly (p < 0.05). Likewise, the severity of ventricular dilatation is lower in minocycline treated hydrocephalic animals compared with the no minocycline group (p < 0.05). CONCLUSION: Minocycline treatment is effective in reducing the gliosis and delaying the development of hydrocephalus with prospective to be the auxiliary therapeutic method of hydrocephalus.