Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. METHODS: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I2-statistics. RESULTS: We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%-84%]; I2=82%), focal neurological deficits 55% ([95% CI, 40%-70%]; I2=82%), encephalopathy 54% ([95% CI, 39%-68%]; I2=43%), seizures 37% ([95% CI, 27%-49%]; I2=65%), headache 31% ([95% CI, 22%-42%]; I2=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%-100%]; I2=44%), lobar cerebral microbleeds 96% ([95% CI, 92%-99%]; I2=25%), gadolinium enhancing lesions 54% ([95% CI, 42%-66%]; I2=62%), cortical superficial siderosis 51% ([95% CI, 34%-68%]; I2=77%) and lobar macrohemorrhage 40% ([95% CI, 11%-73%]; I2=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%-53%]; I2=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. CONCLUSIONS: Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.

Management of neurological complications related to aneurysmal subarachnoid hemorrhage: A comparison of the bedside therapeutic algorithms.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is of the most serious emergencies in neurosurgical practice and continues to be associated with high morbidity and mortality. Beyond securing the ruptured aneurysm to prevent a rebleed, physicians continue to be concerned about potential complications such as cerebral vasospasm-delayed cerebral ischemia (DCI), an area where management remains highly variable. This study aimed at reviewing the most recent literature and assessing any up-to-date schemes for treating the most common aSAH neurological complications in adults that can be applied in daily clinical practice towards optimising outcomes. METHODS: A systematic review was performed according to PRISMA guidelines on the management of aSAH neurological complications in adults. The literature surveyed was between 2016 and 2022 inclusive, using the Pubmed search engine. Comparisons between the methods suggested by existing therapeutic algorithms were discussed. RESULTS: Six stepwise algorithms assisting the decision-making for treating cerebral vasospasm-DCI were recognised and compared. No algorithm was found for the management of any other neurological complications of aSAH. Despite differences in the algorithms, induced hypertension and endovascular therapy were common treatments in all approaches. Controversy in the therapeutic process of these complications surrounds not only the variability of methods but also their optimal application towards clinical outcome optimisation. CONCLUSIONS: A universal approach to managing aSAH complications is lacking. Despite advances in the techniques to secure a ruptured aneurysm, there persist a high rate of neurological deficit and mortality, and several unanswered questions. More research is required towards stratification of current treatment algorithms as per the quality of their evidence.

Prevalence of Clinical and Neuroimaging Markers in Cerebral Amyloid Angiopathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Limited data exist regarding the prevalence of clinical and neuroimaging manifestations among patients diagnosed with cerebral amyloid angiopathy (CAA). We sought to determine the prevalence of clinical phenotypes and radiological markers in patients with CAA. METHODS: Systematic review and meta-analysis of studies including patients with CAA was conducted to primarily assess the prevalence of clinical phenotypes and neuroimaging markers as available in the included studies. Sensitivity analyses were performed based on the (1) retrospective or prospective study design and (2) probable or unspecified CAA status. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using the Cochran Q and I2 statistics. RESULTS: We identified 12 prospective and 34 retrospective studies including 7159 patients with CAA. The pooled prevalence rates were cerebral microbleeds (52% [95% CI, 43%-60%]; I2=93%), cortical superficial siderosis (49% [95% CI, 38%-59%]; I2=95%), dementia or mild cognitive impairment (50% [95% CI, 35%-65%]; I2=97%), intracerebral hemorrhage (ICH; 44% [95% CI, 27%-61%]; I2=98%), transient focal neurological episodes (48%; 10 studies [95% CI, 29%-67%]; I2=97%), lacunar infarcts (30% [95% CI, 25%-36%]; I2=78%), high grades of perivascular spaces located in centrum semiovale (56% [95% CI, 44%-67%]; I2=88%) and basal ganglia (21% [95% CI, 2%-51%]; I2=98%), and white matter hyperintensities with moderate or severe Fazekas score (53% [95% CI, 40%-65%]; I2=91%). The only neuroimaging marker that was associated with higher odds of recurrent ICH was cortical superficial siderosis (odds ratio, 1.57 [95% CI, 1.01-2.46]; I2=47%). Sensitivity analyses demonstrated a higher prevalence of ICH (53% versus 16%; P=0.03) and transient focal neurological episodes (57% versus 17%; P=0.03) among retrospective studies compared with prospective studies. No difference was documented between the prevalence rates based on the CAA status. CONCLUSIONS: Approximately one-half of hospital-based cohort of CAA patients was observed to have cerebral microbleeds, cortical superficial siderosis, mild cognitive impairment, dementia, ICH, or transient focal neurological episodes. Cortical superficial siderosis was the only neuroimaging marker that was associated with higher odds of ICH recurrence. Future population-based studies among well-defined CAA cohorts are warranted to corroborate our findings.

Shunt Over-drainage, Slit Ventricle Syndrome, Programmable Valves and Anti-Siphon Devices. A Narrative Review of a Multifactorial and Intractable Problem.

The current management strategy of hydrocephalus mainly involves the insertion of a ventriculoperitoneal shunt and is inherently related with a complication widely known as shunt over-drainage. Albeit this is a well-recognized complication, the true incidence and severity of this phenomenon remains undefined and most probably underdiagnosed, necessitating a more comprehensive pathophysiologic and therapeutic consideration. The slit ventricle syndrome is intimately related with the entity of shunt over-drainage, although who's the definition of the former is implicated by a lack of universally accepted inclusion criteria. Another point of controversy is related with the absence of widely accepted criteria that would be able to discriminate the existing differentiations between these two entities. This is reflected in the fact that there are many proposed, relevant, treatment protocols. The background for all this data is based on the uncertainty and ambiguity regarding the pathophysiological mechanisms that are implicated. Current efforts are centered on the implementation of precautionary measures, as well as on treatment of both of these entities. Currently, there are enough evidence that support the concept that prevention of siphoning via the use of gravitational valves or antisiphon devices is the most efficacious means contained in our current therapeutic armamentarium. We attempt to present an overview of this complex entity, emphasizing on the hydrodynamics of the cerebrospinal fluid circulation in conditions harboring a ventriculoperitoneal shunt, the effect of the siphoning effect and the role of programmable valves and anti-siphon devices in our effort to eliminate this phenomenon. Based on an extensive literature review and on expert opinion, we concluded that the insertion of an anti-siphon device (gravitational shunt valves) could reliably address the issue of over-drainage, when a patient assumes a vertical position. Besides that, there are ongoing prospective studies centered on the safety and efficacy of adjustable gravitational valves, whose results are of ultimate importance. It is of paramount importance to be recognized that, due to the complexity of the pathophysiology of shunted hydrocephalus, lifelong follow-up of patients with ventriculoperitoneal shunts is necessary.

Prevalence, Characteristics, and Outcomes of Undetermined Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

Background and Purpose: There are scarce data regarding the prevalence, characteristics and outcomes of intracerebral hemorrhage (ICH) of undetermined (unknown or cryptogenic) etiology. We sought to determine the prevalence, radiological characteristics, and clinical outcomes of undetermined ICH. Methods: Systematic review and meta-analysis of studies involving patients with spontaneous ICH was conducted to primarily assess the prevalence and clinical-radiological characteristics of undetermined ICH. Additionally, we assessed the rates for ICH secondary to hypertensive arteriopathy and cerebral amyloid angiopathy. Subgroup analyses were performed based on the use of (1) etiology-oriented ICH classification, (2) detailed neuroimaging, and (3) Boston criteria among patients with cerebral amyloid angiopathy related ICH. We pooled the prevalence rates using random-effects models, and assessed the heterogeneity using Cochran Q and I2 statistics. Results: We identified 24 studies comprising 15 828 spontaneous ICH patients (mean age, 64.8 years; men, 60.8%). The pooled prevalences of hypertensive arteriopathy ICH, undetermined ICH, and cerebral amyloid angiopathy ICH were 50% (95% CI, 43%­58%), 18% (95% CI, 13%­23%), and 12% (95% CI, 7%­17% [P<0.001 between subgroups]). The volume of ICH was the largest in cerebral amyloid angiopathy ICH (24.7 [95% CI, 19.7­29.8] mL), followed by hypertensive arteriopathy ICH (16.2 [95% CI, 10.9­21.5] mL) and undetermined ICH (15.4 [95% CI, 6.2­24.5] mL). Among patients with undetermined ICH, the rates of short-term mortality (within 3 months) and concomitant intraventricular hemorrhage were 33% (95% CI, 25%­42%) and 38% (95% CI, 28%­48%), respectively. Subgroup analysis demonstrated a higher rate of undetermined ICH among studies that did not use an etiology-oriented classification (22% [95% CI, 15%­29%]). No difference was observed between studies based on the completion of detailed neuroimaging to assess the rates of undetermined ICH (P=0.62). Conclusions: The etiology of spontaneous ICH remains unknown or cryptogenic among 1 in 7 patients in studies using etiology-oriented classification and among 1 in 4 patients in studies that avoid using etiology-oriented classification. The short-term mortality in undetermined ICH is high despite the relatively small ICH volume.

Hemicraniectomy for Malignant Middle Cerebral Artery Syndrome: A Review of Functional Outcomes in Two High-Volume Stroke Centers.

BACKGROUND AND PURPOSE: Despite recent landmark randomized controlled trials showing significant benefits for hemicraniectomy (HCT) compared with medical therapy (MT) in patients with malignant middle cerebral artery infarction (MMCAI), HCT rates have not substantially increased in the United States. We sought to evaluate early outcomes in patients with MMCAI who were treated with HCT (cases) in comparison to patients treated with MT due to the perception of procedural futility by families (controls). METHODS: We retrospectively evaluated consecutive patients with acute MMCAI treated in 2 tertiary care centers during a 7-year period. Pretreatment National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at 3 months were documented. Functional independence (FI) and survival without severe disability (SWSD) were defined as mRS of 0-2 and 0-4, respectively. RESULTS: A total of 66 patients (37 cases and 29 controls) fulfilled the study inclusion criteria (mean age 59 ± 15 years, 52% men, median admission NIHSS score: 19 points [interquartile range {IQR}: 16-22]). Cases were younger (51 ± 11 versus 68 ± 13 years; P < .001) and tended to have lower median admission NIHSS than controls (18 [IQR:16-20] versus 20 [IQR:18-23]; P = .072). The rates of FI and SWSD at 3 months were higher in cases than controls (16% versus 0% [P = .031] and 62% versus 0% [P < .001]), while 3-month mortality was lower (24% versus 77%; P < .001). Multivariable Cox regression analyses adjusting for potential confounders identified HCT as the most important predictor of lower risk of 3-month mortality (hazard ratio: .02, 95% confidence interval: .01-0.10; P < .001). CONCLUSIONS: HCT is a critical and effective therapy for patients with MMCAI but cannot provide a guarantee of functional recovery.

The Insertion of Electrodes in the Brain for Electrophysiological Recording or Chronic Stimulation Is Not Associated With Any Biochemically Detectable Neuronal Injury.

OBJECTIVE: The aim of this study was to evaluate the degree of brain tissue injury that could be potentially induced by the introduction of a) microrecording electrodes, b) macrostimulation electrodes, or c) chronic stimulation electrodes. We aimed to evaluate whether the use of five simultaneous microrecording tracks is associated with any brain injury not detectable by conventional imaging such as CT or MRI. MATERIALS AND METHODS: The study included 61 patients who underwent surgery for implantation of 121 DBS leads. In all cases, five simultaneous tracts were utilized for microelectrode recordings. All patients underwent measurements of serum S-100b at specific time points as follows: a) prior to the operation, and b) intraoperatively at specific stages of the procedure: 1) after opening the burr hole, 2) after the insertion of microrecording electrodes, 3) during macrostimulation, 4) at the end of the operation, and 5) on the first postoperative day. RESULTS: The levels of serum S-100B protein remained within the normal range during the entire period of investigation in all patients with the exception of two cases. In both patients, the procedure was complicated by intraparenchymal hemorrhage visible in neuro-imaging. The first patient developed a small intraparenchymal hemorrhage, visible on the postoperative MRI, with no neurological deficit. The second patient experienced a focal epileptic seizure after the insertion of the right DBS chronic lead and the postoperative CT scan revealed a right frontal lobe hemorrhage. CONCLUSION: These results strongly indicate that the insertion of either multiple recording electrodes or the implantation of chronic electrodes in DBS does not increase the risk of brain hemorrhage or of other intracranial complications, and furthermore it does not cause any biochemically detectable brain tissue damage.

Perioperative microdialysis in meningioma surgery: correlation of cerebral metabolites with clinical outcome.

BACKGROUND: Brain tumour resection requires surgical manoeuvres that may cause an ischaemic injury to peritumoral tissue. The aim of the present study was to examine whether putative alterations in peritumoral tissue biochemistry, monitored by microdialysis, correlate with clinical outcome in patients undergoing craniotomy for meningioma resection. METHODS: In 34 patients undergoing meningioma resection (35 % male; mean age ± SD: 54.3 ± 12.1 years), microdialysis measurements were taken perioperatively from peritumoral brain parenchyma. Standard metabolites (glucose, lactate, pyruvate, glycerol and the lactate:pyruvate ratio) were quantified in relation to clinical outcome assessed by the Glasgow Coma Scale (GCS) and the Karnofsky Performance Status scale. RESULTS: Higher postoperative glucose and pyruvate levels were found in patients with a favourable outcome (GCS not deteriorated or Karnofsky score > 80). Multiple logistic regression analysis (age, preoperative physical status, metabolite levels as independent variables) showed that lower postoperative glucose and pyruvate levels as well as higher lactate:pyruvate ratio values were independently associated with an unfavourable outcome as defined by Karnofsky score <80 [(OR: 0.084, 95 % CI: 0.01-0.98, p = 0.049), (OR: 0.97, 95 % CI: 0.95-0.99, p = 0.050), (OR: 1.21, 95 % CI: 1.04-1.42, p = 0.015) respectively], as well as with death [(OR: 0.08, 95 % CI: 0.01-0.97, p = 0.046), (OR: 0.94, 95 % CI: 0.89-0.99, p = 0.016), (OR: 1.07, 95 % CI: 1.00-1.15, p = 0.05) respectively]. CONCLUSIONS: Postoperative levels of glucose and pyruvate and the lactate:pyruvate ratio appear to correlate with clinical outcome in patients undergoing meningioma resection. The present findings provide support for the utility of microdialysis as a prognostic tool in brain tumour surgery.

Intrathecal baclofen associated with improvement of consciousness disorders in spasticity patients.

OBJECTIVE: Intrathecal baclofen (ITB) pump is a therapeutic option for persistent vegetative state and minimal conscious state patients that have associated spasticity. We investigated whether this treatment modality can affect their level of consciousness. METHOD: In this prospective, open label, observational study, we implanted ITB pumps for the treatment of spasticity in eight patients with disorders of consciousness (vegetative state and minimally conscious state) and we followed them with the Coma Recovery Scale-Revised, the Eastern Cooperative Oncology Group (ECOG) performance scale, and the Modified Ashworth spasticity scale. Baclofen dose and complications also were noted. RESULTS: The offending pathologies were traumatic brain injury in six, anoxia due to cardiac arrest in one, acute obstructive hydrocephalus in one. Two of the patients showed a marked, persistent improvement that fulfilled the criteria of emergence from minimally conscious state. Two of patients had their ITB pumps prematurely removed because of complications. The ECOG score was 4 for all patients and did not change during the study. CONCLUSION: ITB might be associated with a significant improvement in the disorder of consciousness of two patients from a total of six that had a chronic ITB treatment.

Chronic Pediatric Headache as a Manifestation of Shunt Over-Drainage and Slit Ventricle Syndrome in Patients Harboring a Cerebrospinal Fluid Diversion System: A Narrative Literature Review.

The main subject of the current review is a specific subtype of headache, which is related to shunt over-drainage and slit ventricle syndrome, in pediatric patients harboring an implanted shunt device for the management of hydrocephalus. This clinical entity, along with its impairment regarding the quality of life of the affected individuals, is generally underestimated. This is partly due to the absence of universally agreed-upon diagnostic criteria, as well as due to a misunderstanding of the interactions among the implicated pathophysiological mechanisms. A lot of attempts have been performed to propose an integrative model, aiming at the determination of all the offending mechanisms of the shunt over-drainage syndrome, as well as the determination of all the clinical characteristics and related symptomatology that accompany these secondary headaches. This subcategory of headache, named postural dependent headache, can be associated with nausea, vomiting, and/or radiological signs of slim ventricles and/or subdural collections. The ultimate goal of our review is to draw clinicians' attention, especially that of those that are managing pediatric patients with permanent, long-standing, ventriculoperitoneal, or, less commonly, ventriculoatrial shunts. We attempted to elucidate all clinical and neurological characteristics that are inherently related to this type of headache, as well as to highlight the current management options. This specific subgroup of patients may eventually suffer from severe, intractable headaches, which may negatively impair their quality of daily living. In the absence of any other clinical condition that could be incriminated as the cause of the headache, shunt over-drainage should not be overlooked. On the contrary, it should be seriously taken into consideration, and its management should be added to the therapeutic armamentarium of such cases, which are difficult to be handled.

Emerging Role of the Slit/Roundabout (Robo) Signaling Pathway in Glioma Pathogenesis and Potential Therapeutic Options.

Gliomas represent the most common primary Central Nervous System (CNS) tumors, characterized by increased heterogeneity, dysregulated intracellular signaling, extremely invasive properties, and a dismal prognosis. They are generally resistant to existing therapies and only a few molecular targeting options are currently available. In search of signal transduction pathways with a potential impact in glioma growth and immunotherapy, the Slit guidance ligands (Slits) and their Roundabout (Robo) family of receptors have been revealed as key regulators of tumor cells and their microenvironment. Recent evidence indicates the implication of the Slit/Robo signaling pathway in inflammation, cell migration, angiogenesis, and immune cell infiltration of gliomas, suppressing or promoting the expression of pivotal proteins, such as cell adhesion molecules, matrix metalloproteinases, interleukins, angiogenic growth factors, and immune checkpoints. Herein, we discuss recent data on the significant implication of the Slit/Robo signaling pathway in glioma pathology along with the respective targeting options, including immunotherapy, monoclonal antibody therapy, and protein expression modifiers.

CSF and plasma biomarkers in cerebral amyloid angiopathy: A single-center study and a systematic review/meta-analysis.

INTRODUCTION: There are limited data regarding cerebrospinal fluid (CSF) and plasma biomarkers among patients with Cerebral Amyloid Angiopathy (CAA). We sought to investigate the levels of four biomarkers [ß-amyloids (Aß42 and Aß40), total tau (tau) and phosphorylated tau (p-tau)] in CAA patients compared to healthy controls (HC) and patients with Alzheimer Disease (AD). PATIENTS AND METHODS: A systematic review and meta-analysis of published studies, including also a 5 year single-center cohort study, with available data on CSF and plasma biomarkers in symptomatic sporadic CAA versus HC and AD was conducted. Biomarkers' comparisons were investigated using random-effects models based on the ratio of mean (RoM) biomarker concentrations. RoM < 1 and RoM > 1 indicate lower and higher biomarker concentration in CAA compared to another population, respectively. RESULTS: We identified nine cohorts, comprising 327 CAA patients (mean age: 71 ± 5 years; women: 45%) versus 336 HC (mean age: 65 ± 5 years; women: 45%) and 384 AD patients (mean age: 68 ± 3 years; women: 53%) with available data on CSF biomarkers. CSF Aß42 levels [RoM: 0.47; 95% CI: 0.36-0.62; p < 0.0001], Aß40 levels [RoM: 0.70; 95% CI: 0.63-0.79; p < 0.0001] and the ratio Aß42/Aß40 [RoM: 0.62; 95% CI: 0.39-0.98; p = 0.0438] differentiated CAA from HC. CSF Aß40 levels [RoM: 0.73; 95% CI: 0.64-0.83; p = 0.0003] differentiated CAA from AD. CSF tau and p-tau levels differentiated CAA from HC [RoM: 1.71; 95% CI: 1.41-2.09; p = 0.0002 and RoM: 1.44; 95% CI: 1.20-1.73; p = 0.0014, respectively] and from AD [RoM: 0.65; 95% CI: 0.58-0.72; p < 0.0001 and RoM: 0.64; 95% CI: 0.57-0.71; p < 0.0001, respectively]. Plasma Aß42 [RoM: 1.14; 95% CI: 0.89-1.45; p = 0.2079] and Aß40 [RoM: 1.07; 95% CI: 0.91-1.25; p = 0.3306] levels were comparable between CAA and HC. CONCLUSIONS: CAA is characterized by a distinct CSF biomarker pattern compared to HC and AD. CSF Aß40 levels are lower in CAA compared to HC and AD, while tau and p-tau levels are higher in CAA compared to HC, but lower in comparison to AD patients.

Age and gender disparities in the risk of carotid revascularization procedures.

The potential effect of age and gender stratification in the outcome of patients with carotid artery stenosis undergoing carotid revascularization procedures (CRP) may have important implications in clinical practice. Both European Stroke Organization and American Heart Association guidelines suggest that age and sex should be taken into account when selecting a CRP for an individual patient. We reviewed available literature data through Medline and Embase. Our search was based on the combination of terms: age, gender, sex, carotid artery stenosis, carotid artery stenting (CAS) and carotid endarterectomy (CEA). Postoperative stroke and mortality rates increased with age after any CRP (CEA or CAS), especially in patients aged over 75 years. Older patients with carotid artery stenosis undergoing CAS were found to have a nearly double risk of stroke or death compared with CEA, while CEA was found to benefit more patients aged over 70 years with symptomatic carotid artery stenosis. Male patients with symptomatic or asymptomatic carotid artery stenosis had lower stroke/mortality rates and benefited more from CEA compared with females. For the periprocedural risk of stroke or death in patients with carotid artery stenosis after CAS no sex differences were found. Therefore, CEA appears to have lower perioperative risks than CAS in patients aged over 70 years, and thus should be the treatment of choice if not contraindicated. The periprocedural risk of CEA is lower in men than in women, while there was no effect of gender on the periprocedural risk of CAS.

Posterior spinal decompression in adults with spinal cord injury without traumatic compromise of the spinal canal: what is the data?

Background: Spinal cord injury (SCI) can be caused by a variety of factors and its severity can range from a mild concussion to a complete severing of the spinal cord. Τreatment depends on the type and severity of injury, the patient's age and overall health. Reduction of dislocated or fractured vertebrae via closed manipulation or surgical procedures, fixation and removal of bony fragments and debris that compromise the spinal canal are indicated for decompression of the spinal cord and stabilization of the spine. However, when there is no obvious traumatic obstruction of spinal canal, the question arises as to whether laminectomy is needed to be performed to improve neurological outcome. Methods: A literature review covering all indexed studies published between 2013 and 2023 was performed using keywords to identify the patient group of interest (spinal cord injury, SCI, spinal cord trauma, cervical, thoracic, lumbar, thoracolumbar),central cord syndrome (CCS) and the interventions (laminectomy, laminoplasty, decompression, duroplasty). Results: This review includes6 observational studies investigating the outcome of posterior spinal decompression in patients suffering from spinal cord injury without traumatic spinal cord stenosis. Most patients already had degenerative stenosis. From a total of 202, 151 patients (74.7%) improved neurologically by at least one grade at ASIA scale, after being treated with either laminectomy, laminoplasty, duroplasty or a combination of these techniques. Conclusion: Early decompression in SCI patients remains a reasonable practice option and can be performed safely, but no specific evidence supports the use of laminectomy alone. There is emerging evidence that intended durotomy followed by extended meningoplasty may improve the neurological outcome in patients suffering from SCI when meta-traumatic edema is apparent. However, the lack of high-quality evidence and results support the need for further research.

Radiation-induced meningiomas (RIM) in adults: A single-centre retrospective experience.

Introduction: Radiotherapy of central nervous system (CNS) is treatment against many paediatric cancers, even if it is a well-recognized risk factor for meningioma formation. An increased risk of developing secondary brain tumors like radiation-induced meningiomas (RIM) is related to irradiated patients. Research question: This retrospective study aims to present RIM cases treated in a single tertiary-hospital in Greece and compare the results with international literature and cases of sporadic meningiomas. Materials and methods: A single-centre retrospective study of all patients diagnosed between January 2012 and September 2022 with RIM after having been irradiated in CNS for paediatric cancer was undertaken through hospital's electronic record and clinical notes, identifying baseline demographics and latency period. Results: Thirteen patients were identified with RIM diagnosis after receiving irradiation for Acute Lymphoblastic Leukaemia (69.2%), Premature Neuro-Ectodermal Tumour (23.1%), and Astrocytoma (7.7%). Median age at irradiation was 5 years old and 32 years old at RIM's presentation. The latent period from irradiation to meningioma diagnosis was 26.23 â€‹± â€‹5.96 years. After surgical excision, histopathologic results showed grade I meningiomas in 12 out of thirteen cases, while only one atypical meningioma was diagnosed. Conclusion: Patients who underwent CNS-radiotherapy in childhood for any condition have an increased risk of developing secondary brain tumors such as radiation-induced meningiomas. RIMs resemble sporadic meningiomas in symptomatology, location, treatment, and histologic grade. However, long-term follow-up and regular check-ups are recommended in irradiated patients due to short latency period from irradiation to RIM development, which means younger age patients than those with sporadic meningiomas cases.

Glioma Cells Expressing High Levels of ALDH5A1 Exhibit Enhanced Migration Transcriptional Signature in Patient Tumors.

Accumulating data shows that altered metabolic activity contributes to glioma development. Recently, modulation of SSADH (succinic semialdehyde dehydrogenase) expression, implicated in the catabolism of GABA neurotransmitter, was shown to impact glioma cell properties, such as proliferation, self-renewal and tumorigenicity. The purpose of this study was to investigate the clinical significance of SSADH expression in human gliomas. Using public single-cell RNA-sequencing data from glioma surgical resections, we initially grouped cancer cells according to ALDH5A1 (Aldehyde dehydrogenase 5 family member A1) expression, which encodes SSADH. Gene ontology enrichment analysis of genes differentially expressed between cancer cells expressing high or low levels of ALDH5A1, highlighted enrichment in genes implicated in cell morphogenesis and motility. In glioblastoma cell lines, ALDH5A1 knockdown inhibited cell proliferation, induced apoptosis and reduced their migratory potential. This was accompanied by a reduction in the mRNA levels of the adherens junction molecule ADAM-15 and deregulation in the expression of EMT biomarkers, with increased CDH1 and decreased vimentin mRNA levels. Evaluation of SSADH expression in a cohort of 95 gliomas using immunohistochemistry showed that SSADH expression was significantly elevated in cancer tissues compared to normal brain tissues, without any significant correlation with clinicopathological characteristics. In summary, our data show that SSADH is upregulated in glioma tissues irrespective of the histological grade and its expression sustains glioma cell motility.

Expression of interleukin-8 receptor CXCR2 and suppressor of cytokine signaling-3 in astrocytic tumors.

The aim was to expand recently published information regarding the significance of the interleukin (IL)-8/p-STAT-3 (signal transducer and activator of transcription) pathway in astrocytomas, focusing on the IL-8 receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and the STAT-3 inhibitor SOCS-3 (suppressors of cytokine signaling). A total of 91 paraffin-embedded human astrocytoma tissues (grades II-IV) were investigated for the association of SOCS-3 and CXCR2 expression with clinicopathologic and morphometric microvascular characteristics, vascular endothelial growth factor (VEGF), IL-8 and p-STAT-3 expression and patient survival. Peripheral IL-8 secretion levels were assessed by enzyme-linked immunosorbent spot (ELISPOT). SOCS-3, p-STAT-3 and CXCR2 protein levels were also quantified by Western immunoblotting in six cases, and the protein levels of SOCS-3 and CXCR2 were correlated with the immunohistochemical expression of the respective proteins. All CXCR2-positive cases by Western immunoblotting displayed increased peripheral IL-8 secretion levels. Treatment of primary glioblastoma cell cultures with exogenous IL-8 enhanced proliferation, and this effect was inhibited by treatment with a neutralizing anti-CXCR2 antibody. SOCS-3 and CXCR2 were expressed by neoplastic astrocytes in 92.4% and 48.78% of cases, respectively, with their levels increasing with histological grade and extent of necrosis. VEGF expression and microvessel density, CXCR2 and IL-8 levels were interrelated. SOCS-3 and p-STAT-3 were co-expressed in 85.7% of cases, although they were not interrelated. In univariate survival analysis, increased SOCS-3 expression and the presence of CXCR2 adversely affected survival, whereas in multivariate analysis, only CXCR2 remained significant. The prognostic significance of CXCR2 was validated in an independent set of 63 patients. Our data implicate IL-8/CXCR2 signaling pathway in the progression and regulation of angiogenesis in astrocytomas and provide a rationale for CXCR2 therapeutic exploitation in these tumors.

Phosphorylated 4E-binding protein 1 (p-4E-BP1): a novel prognostic marker in human astrocytomas.

AIMS: To investigate the significance of the mammalian target of rapamycin (mTOR) pathway in astrocytic tumours, published information in this context being limited, especially regarding phosphorylated 4E-binding protein (p-4E-BP) 1. METHODS AND RESULTS: Paraffin-embedded tissue from 111 patients with astroglial tumours (grades II-IV) was investigated for the association of phosphorylated mTOR (p-mTOR) signalling components with phosphorylated extracellular signal-related kinase 1/2 (p-ERK1/2) and phosphorylated AKT (p-AKT) expression, clinicopathological features, angiogenesis, isocitrate dehydrogenase 1 (IDH1)-R132H, and survival. Expression was also quantified by western blot analysis in 12 cases and in three primary glioma cell cultures following rapamycin treatment. p-mTOR expression correlated with p-4E-BP1 expression and marginally with p-p70S6K expression. p-4E-BP1 expression increased with tumour grade. Rapamycin induced a decline in phosphorylation levels of all three proteins. Nuclear p-AKT and cytoplasmic p-ERK1/2 immunoexpression correlated with p-4E-BP1 expression, whereas cytoplasmic p-AKT expression correlated with p-p70S6K expression. All three proteins were associated with increased angiogenesis but not with IDH1-R132H expression status. p-mTOR adversely affected overall and disease-free survival in univariate analysis. In multivariate survival analysis, the presence of p-4E-BP1 predicted shortened overall survival in the entire cohort and glioblastomas. CONCLUSIONS: mTOR signalling components are differentially involved in the acquisition of a more aggressive and angiogenic phenotype in astrocytic tumours. Moreover, p-4E-BP1 emerges as a novel prognostic marker, which might aid in the selection of patients who are more likely to benefit from therapy with mTOR inhibitors.

The Role of Antisiphon Devices in the Prevention of Central Ventricular Catheter Obliteration for Hydrocephalus: A 15-Years Institution's Experience Retrospective Analysis.

Shunt over-drainage in patients harboring a ventriculoperitoneal shunt constitutes one of the most devastating, and difficult to manage, side effects associated with this operation. Siphoning is one of the most important contributing factors that predispose to this complication. Based on the fact that the predisposing pathophysiologic mechanism is considerably multiplicated, amelioration of that adverse condition is considerably difficult to achieve. A lot of evidence suggests that the widespread utilization of gravitational valves or antisiphon devices is of utmost importance, in order to minimize or even avoid the occurrence of such complications. The recent literature data highlight that gravity-related, long-lasting shunt over-drainage consists of a momentous factor that could be considered one of the main culprits of central shunt failure. A lot of efforts have been performed, in order to design effective means that are aimed at annihilating siphoning. Our tenet was the investigation of the usefulness of the incorporation of an extra apparatus in the shunt system, capable of eliminating the impact of the siphoning effect, based on the experience that was gained by their long-term use in our institution. A retrospective analysis was performed, based on the data that were derived from our institution's database, centered on patients to which an ASD was incorporated into their initial shunt device between 2006 and 2021. A combination of clinical, surgical, radiological findings, along with the relevant demographic characteristics of the patients were collected and analyzed. We attempted to compare the rates of shunt dysfunction, attributed to occlusion of the ventricular catheter, in a group of patients, before and after the incorporation of an anti-siphon device to all of them. A total number of 120 patients who have already been shunted due to hydrocephalus of different etiologies, were managed with the insertion of an ASD. These devices were inserted at different anatomical locations, which were located peripherally to the initially inserted valvular mechanism. The data that were collected from a subpopulation of 17 of these patients were subjected to a separate statistical analysis because they underwent a disproportionately large number of operations (i.e., >10-lifetime shunt revisions). These patients were studied separately as their medical records were complicated. The analysis of our records revealed that the secondary implementation of an ASD resulted in a decrease of the 1-year and 5-year central catheter dysfunction rates in all of our patients when compared with the relevant obstruction rates at the same time points prior to ASD insertion. According to our data, and in concordance with a lot of current literature reports, an ASD may offer a significant reduction in the obstruction rates that is related to the ventricular catheter of the shunt. These data could only be considered preliminary and need to be confirmed with prospective studies. Nevertheless, this study could be considered capable of providing supportive evidence that chronic shunt over-drainage is a crucial factor in the pathophysiology of shunt malfunction. Apart from that, it could provide pilot data that could be reviewed in order to organize further clinical and laboratory studies, aiming toward the assessment of optimal shunt valve systems that, along with ASD, resist siphoning.

The Entity of Cerebellar Mutism Syndrome: A Narrative Review Centered on the Etiology, Diagnostics, Prevention, and Therapeutic Options.

Cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome, is an entity that entails a constellation of signs and symptoms which are recorded in a limited number of pediatric patients who have been operated on mainly for tumors involving the posterior cranial fossa, and more precisely, the region of the vermis. Medulloblastoma seems to constitute the most commonly recognized pathological substrate, associated with this entity. The most prevalent constituents of this syndrome are noted to be a, often transient, although protracted, language impairment, emotional lability, along with cerebellar and brainstem dysfunction. Apart from that, a definite proportion of involved individuals are affected by irreversible neurological defects and long-lasting neurocognitive impairment. A bulk of literature and evidence based on clinical trials exist, which reflect the continuous effort of the scientific community to highlight all perspectives of this complex phenomenon. There are several circumstances that intervene in our effort to delineate the divergent parameters that constitute the spectrum of this syndrome. In summary, this is implicated by the fact that inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty regarding risk factors and etiology are all constituents of a non-well-investigated syndrome. Currently, a preliminary consensus exists about the identification of a group of diagnostic prerequisites that are managed as sine qua non, in our aim to document the diagnosis of CMS. These include language impairment and emotional lability, as proposed by the international Board of the Posterior Fossa Society in their consensus statement. It is common concept that midline tumor location, diagnosis of medulloblastoma, younger age at diagnosis, and preoperatively established language impairment should be accepted as the most determinant predisposing conditions for the establishment of this syndrome. A well-recognized pathophysiological explanation of CMS includes disruption of the cerebellar outflow tracts, the cerebellar nuclei, and their efferent projections through the superior cerebellar peduncle. Despite the relative advancement that is recorded regarding the diagnostic section of this disease, no corresponding encouraging results are reported, regarding the available treatment options. On the contrary, it is mainly targeted toward the symptomatic relief of the affected individuals. The basic tenet of our review is centered on the presentation of a report that is dedicated to the definition of CMS etiology, diagnosis, risk factors, clinical presentation, and clinical management. Apart from that, an effort is made that attempts to elucidate the paramount priorities of the scientific forum, which are directed toward the expansion our knowledge in the era of diagnostics, prevention, and therapeutic options for patients suffering from CM, or who are at risk for development of this syndrome.