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1.
Front Hum Neurosci ; 16: 950434, 2022.
Article in English | MEDLINE | ID: mdl-36158622

ABSTRACT

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson's disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings in eight patients with advanced Parkinson's disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (ρ = -0.81, p < 0.0218, Spearman's correlation coefficient) between left side local field potentials of the low beta band (11-20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface.

2.
Pediatr Neurosurg ; 57(5): 358-364, 2022.
Article in English | MEDLINE | ID: mdl-35988537

ABSTRACT

INTRODUCTION: Intradiploic pseudomeningoceles, also called intradiploic cerebrospinal fluid (CSF) fistulas, are abnormal CSF collections between the two bony tables of the calvaria resulting from postsurgical CSF leakage. To date, only six cases of intradiploic pseudomeningocele have been reported, all occurring in the occipital area. In this paper, we report the seventh case of late-onset occipital intradiploic pseudomeningocele (OIP) occurring in a young female patient who underwent surgery for the removal of a cerebellar pilocytic astrocytoma. In this regard, we also review the literature on the few recognized cases of OIP. CASE PRESENTATION: The case of an 18-year-old female patient known to our institute for an operation 12 years earlier to remove a pilocytic astrocytoma is illustrated. At admission, the patient complained only of occasional orthostatic headache. Brain imaging demonstrated a pseudomeningocele extended intradiploically from the occipital squama to the condylar and clivus regions, thinning both occipital bone tables and dilating the CSF-filled diploe. Watertight duroplasty and cranioplasty were effectively performed. CONCLUSION: Pediatric patients undergoing posterior cranial fossa craniotomy/craniectomy may postoperatively develop OIP. In this setting, treatment of any dural CSF fistula should be considered because of the risk of progressive extension and bone erosion.


Subject(s)
Astrocytoma , Cranial Fossa, Posterior , Humans , Female , Child , Adolescent , Cranial Fossa, Posterior/diagnostic imaging , Cranial Fossa, Posterior/surgery , Cerebrospinal Fluid Leak/etiology , Occipital Bone/diagnostic imaging , Occipital Bone/surgery , Craniotomy/adverse effects , Craniotomy/methods , Astrocytoma/surgery , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Postoperative Complications/surgery
3.
Clin Neurophysiol ; 133: 29-38, 2022 01.
Article in English | MEDLINE | ID: mdl-34794045

ABSTRACT

OBJECTIVES: To evaluate spectra and their correlations with clinical symptoms of local field potentials (LFP) acquired from wide- and close-spaced contacts (i.e. between contacts 0-3 or LFP03, and contacts 1-2 or LFP12 respectively) on the same DBS electrode within the subthalamus (STN) in Parkinson's disease (PD), before and after levodopa administration. METHODS: LFP12 and LFP03 were recorded from 20 PD patients. We evaluated oscillatory power, local and switched phase-amplitude coupling (l- and Sw-PAC) and correlation with motor symptoms (UPDRSIII). RESULTS: Before levodopa, both LFP03 and LFP12 power in the α band inversely correlated with UPDRSIII. Differences between contacts were found in the low-frequency bands power. After levodopa, differences in UPDRSIII were associated to changes in LFP03 low-ß and LFP12 HFO (high frequency oscillations, 250-350 Hz) power, while a modulation of the low-ß power and an increased ß-LFO (low frequency oscillations, 15-45 Hz) PAC was found only for LFP12. CONCLUSION: This study reveals differences in spectral pattern between LFP12 and LFP03 before and after levodopa administration, as well as different correlations with PD motor symptoms. SIGNIFICANCE: Differences between LFP12 and LFP03 may offer an opportunity for optimizing adaptive deep brain stimulation (aDBS) protocols for PD. LFP12 can be used to detect ß-HFO coupling and ß power (i.e. bradykinesia), while LFP03 are optimal for low frequency oscillations (dyskinesias).


Subject(s)
Membrane Potentials/physiology , Parkinson Disease/physiopathology , Subthalamic Nucleus/physiopathology , Adult , Aged , Antiparkinson Agents/pharmacology , Antiparkinson Agents/therapeutic use , Deep Brain Stimulation , Electrodes, Implanted , Female , Humans , Levodopa/pharmacology , Levodopa/therapeutic use , Male , Membrane Potentials/drug effects , Middle Aged , Parkinson Disease/drug therapy , Subthalamic Nucleus/drug effects
4.
Front Neurosci ; 15: 763235, 2021.
Article in English | MEDLINE | ID: mdl-34949982

ABSTRACT

Deep brain stimulation (DBS) is used for the treatment of movement disorders, including Parkinson's disease, dystonia, and essential tremor, and has shown clinical benefits in other brain disorders. A natural path for the improvement of this technique is to continuously observe the stimulation effects on patient symptoms and neurophysiological markers. This requires the evolution of conventional deep brain stimulators to bidirectional interfaces, able to record, process, store, and wirelessly communicate neural signals in a robust and reliable fashion. Here, we present the architecture, design, and first use of an implantable stimulation and sensing interface (AlphaDBSR System) characterized by artifact-free recording and distributed data management protocols. Its application in three patients with Parkinson's disease (clinical trial n. NCT04681534) is shown as a proof of functioning of a clinically viable implanted brain-computer interface (BCI) for adaptive DBS. Reliable artifact free-recordings, and chronic long-term data and neural signal management are in place.

5.
Front Neurol ; 12: 643841, 2021.
Article in English | MEDLINE | ID: mdl-34135846

ABSTRACT

Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans. Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS. Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition. Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p < 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation). Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS.

6.
J Orthop Res ; 39(7): 1479-1495, 2021 07.
Article in English | MEDLINE | ID: mdl-32779775

ABSTRACT

The etiology of intervertebral disc degeneration is largely unknown, but local neuroinflammation may exert a crucial role through activation of cells as microglia and pro-inflammatory cytokines production. We aimed to compare the effect of degenerated and normal intervertebral disc microenvironment on microglial cells and the potential role of sphingosine-1-phosphate, a pro-inflammatory sphingolipid, in their crosstalk. Human degenerated intervertebral discs (Pfirrmann grade IV) were obtained at surgery for spondylolisthesis. Normal intervertebral discs were collected from cadaveric normal lumbar spines. Normal and degenerated-intervertebral discs were kept in culture to obtain media conditioning. Then, microglial cells were cocultured with conditioned media and viability, proliferation, migration, chemotaxis, and inflammatory gene expression were evaluated. The results demonstrate that conditioned media from degenerated intervertebral discs activate microglial cells, increasing chemotaxis, migration, and pro-inflammatory mediators release to a great extent than normal discs. In addition, we show that the administration of sphingosine-1-phosphate to normal intervertebral disc/microglia coculture mimicked degenerative effects. Interestingly, sphingosine-1-phosphate content in conditioned media from degenerated discs was significantly higher than that from normal ones. In addition, FTY720, a functional antagonist of sphingosine-1-phosphate, potently inhibited the effect of degenerated intervertebral discs on microglial inflammatory factor transcription and migration. Our data report, for the first time, that sphingosine-1-phosphate is involved as signal in the microenvironment of human degenerated intervertebral discs. Sphingosine-1-phosphate signaling modulation by FTY720 may induce beneficial effects in counteracting microglial activation during intervertebral disc degeneration.


Subject(s)
Intervertebral Disc Degeneration/metabolism , Lysophospholipids/metabolism , Microglia/metabolism , Sphingosine/analogs & derivatives , Animals , Cell Line , Cellular Microenvironment , Chemotaxis , Female , Humans , Male , Mice , Middle Aged , Nitric Oxide/metabolism , Receptor Cross-Talk , Sphingosine/metabolism
7.
Acta Biomed ; 91(10-S): e2020004, 2020 09 23.
Article in English | MEDLINE | ID: mdl-33245073

ABSTRACT

There are no clear guidelines about the treatment Pial Arteriovenous Fistulae (PAVF). For high-risk and severally symptomatic fistulae surgery is the first choice of treatment, including feeding artery ligation, surgical resection, radiosurgery and endovascular embolization techniques. We described a case of a patient with a symptomatic PAVF at the craniocervical junction fed by the anterior spinal artery, successfully treated with endovascular approach consisting of glue embolization of the feeding vessel.


Subject(s)
Arteriovenous Fistula , Embolization, Therapeutic , Endovascular Procedures , Arteries , Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/therapy , Humans , Treatment Outcome
8.
Pituitary ; 23(5): 552-557, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32562134

ABSTRACT

PURPOSE: The aim of the present study is to assess the predictive value of the suprasellar volume (SSV) of nonfunctioning pituitary adenomas (NFPAs) for visual field (VF) impairment in order to guide clinical decision-making and improve neurosurgical management. METHODS: Two independent samples of patients with NFPAs (exploratory population N = 50, testing population N = 98) were included in the present study. In the first phase, we determined the optimal cut-off value of the SSV correlating with VF deficits in the exploratory population. In the second phase, we then studied the accuracy of identified cut-off in predicting a VF deficit in the testing population. RESULTS: In the exploratory population, the optimal cut-off value of the SSV to determine the presence of a VF deficit was 1.5 mL. Sensitivity and specificity of the cut-off were 81.3 and 100%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 100 and 75%, respectively. When we checked the identified cut-off score on the testing population, we found a sensitivity of 71% and a specificity of 100%. The PPV and NPV were 100 and 59.2%, respectively. In six cases with VF defects and SSV inferior to 1.5 mL, the displacement of optic chiasm was in superior position. CONCLUSION: The SSV may represent an accurate method in routinely clinical practice for predicting VF deficit in patients affected by NFPA.


Subject(s)
Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pituitary Neoplasms/physiopathology , Retrospective Studies , Visual Field Tests , Visual Fields/physiology
9.
Cells ; 9(2)2020 01 25.
Article in English | MEDLINE | ID: mdl-31991805

ABSTRACT

: Circulating platelets (PLTs) are able to affect glioblastoma (GBM) microenvironment by supplying oncopromoter and pro-angiogenic factors. Among these mediators, sphingosine-1-phophate (S1P) has emerged as a potent bioactive lipid enhancing cell proliferation and survival. Here, we investigated the effect of "tumor education", characterizing PLTs from GBM patients in terms of activation state, protein content, and pro-angiogenic potential. PLTs from healthy donors (HD-PLTs) and GBM patients (GBM-PLTs) were collected, activated, and analyzed by flow cytometry, immunofluorescence, and Western blotting. To assess the pro-angiogenic contribution of GBM-PLTs, a functional cord formation assay was performed on GBM endothelial cells (GECs) with PLT-releasate. GBM-PLTs expressed higher positivity for P-selectin compared to HD-PLTs, both in basal conditions and after stimulation with adenosine triphosphate (ADP) and thrombin receptor activating peptide (TRAP). PLTs showed higher expression of VEGFR-1, VEGFR-2, VWF, S1P, S1PR1, SphK1, and SPNS. Interestingly, increased concentrations of VEGF and its receptors VEGFR1 and VEGFR2, VWF, and S1P were found in GBM-PLT-releasate with respect to HD-PLTs. Finally, GBM-PLT-releasate showed a pro-angiogenic effect on GECs, increasing the vascular network's complexity. Overall, our results demonstrated the contribution of PLTs to GBM angiogenesis and aggressiveness, advancing the potential of an anti-PLT therapy and the usefulness of PLT cargo as predictive and monitoring biomarkers.


Subject(s)
Biomarkers, Tumor/metabolism , Blood Platelets/metabolism , Brain Neoplasms/metabolism , Glioblastoma/metabolism , Neovascularization, Pathologic/metabolism , Sphingosine-1-Phosphate Receptors/metabolism , Adenosine Diphosphate/pharmacology , Adult , Aged , Blood Platelets/drug effects , Blood Platelets/pathology , Brain Neoplasms/pathology , Cells, Cultured , Endothelial Cells/metabolism , Female , Glioblastoma/pathology , Humans , Male , Middle Aged , Peptide Fragments/pharmacology , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Platelet Membrane Glycoproteins/metabolism , Prognosis , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism
10.
Acta Neurochir (Wien) ; 162(4): 803-812, 2020 04.
Article in English | MEDLINE | ID: mdl-31993749

ABSTRACT

BACKGROUND: Patients affected by a high-grade glioma (HGG) have a poor prognosis with a median survival of 12-16 months. Such poor prognosis affects the perception of the remaining life by patients and the neuropsychological status can strongly affect every-day functioning of these patients. Monitoring changes of neuropsychological functioning (NPF) overtime may provide better clinical information and optimize the neuro-oncological management. The aims of our work were (1) to investigate the feasibility of a complex neuropsychological battery in HGG patients before and during follow-up after surgery; (2) to study the neuropsychological profile of patients affected by HGGs and their relation with the disease status (relapse/death) across time after surgery. METHODS: One hundred two patients who received surgery for HGG between 2011 and 2017 were studied. All clinical data were prospectively recorded. NPF was assessed during the neuro-oncological follow-up through the Milano-Bicocca Battery (MIBIB). Statistical analysis was performed on the neuropsychological results of the tests administered. RESULTS: First, MIBIB proved to be suitable for patients with HGG tumors before and after surgery, and during long-term follow-up; it also showed a cluster structure representative of the principal cognitive domains. Second, we found a steep decline in the neuropsychological profile before death and/or tumor relapse for the 52% of the neuropsychological tests administered. CONCLUSION: Complex neuropsychological batteries can be administered to HGG patients before and during follow-up after surgery. There is a correlation between neuropsychological deterioration and tumor relapse and/or death, which may reflect a progressive damage to cognitive functions due to tumor infiltration and progression.


Subject(s)
Brain Neoplasms/psychology , Brain Neoplasms/surgery , Cognition , Glioma/psychology , Glioma/surgery , Neuropsychological Tests , Postoperative Complications/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/mortality , Cognitive Dysfunction , Feasibility Studies , Female , Follow-Up Studies , Glioma/mortality , Humans , Male , Middle Aged , Negative Results , Neoplasm Recurrence, Local , Predictive Value of Tests , Treatment Outcome , Young Adult
11.
J Neurosurg Sci ; 64(1): 107-112, 2020 Feb.
Article in English | MEDLINE | ID: mdl-26745494

ABSTRACT

Pineal tumors are rare, about 1% of all intracranial tumors. At variance with pineocytomas, usually characterized by a good prognosis, papillary tumors behave more aggressively. Owing to their rarity, little is known about their biology and clinical behavior, moreover conflicting data on prognosis have been reported. Here we present an unusual case of papillary neuroepithelial tumor of the pineal region in a 40-year-old man who was admitted in a state of unconsciousness due to the presence of intracranial hemorrhage. After 21 days from admission, he underwent third ventriculostomy for hydrocephalus and biopsy of the lesion. Since bleeding manifestations are uncommonly associated with this kind of tumors, we performed some additional non routine laboratory tests in order to identify biological indicators of disease course and abnormal angiogenesis. Coagulation screening tests were performed to rule out the presence of coagulopathy and vascular endothelial growth factor (VEGF ) levels were measured in plasma as marker of tumor angiogenic potential. Histologic evaluation confirmed the diagnosis of a papillary tumor of the pineal region with the presence of tiny vessel lumens that may account for increased angiogenesis Coagulation screening was normal and VEGF levels were extremely high if compared to healthy individuals. After 20 months of follow-up the tumor mass, radiotherapy treated, appeared dramatically reduced at MRI evaluation, and, interestingly, VEGF levels, although still higher than in healthy individuals, resulted significantly decreased as compared to those measured at time of first hospital admission suggesting a role for VEGF as indicator of tumor aggressiveness. In conclusion, measurement of angiogenesis circulating soluble markers could have an additional feedback in the diagnosis, therapy and monitoring the disease in patients with very rare CNS tumors as papillary tumors of pineal region that have non univocal clinical behavior and prognosis.


Subject(s)
Biomarkers, Tumor/blood , Intracranial Hemorrhages/etiology , Neoplasms, Neuroepithelial/pathology , Neovascularization, Pathologic/pathology , Pinealoma/pathology , Vascular Endothelial Growth Factor A/blood , Adult , Humans , Male , Neoplasms, Neuroepithelial/blood , Neoplasms, Neuroepithelial/complications , Neovascularization, Pathologic/blood , Pinealoma/blood , Pinealoma/complications
12.
J Neurosurg ; : 1-11, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-31731265

ABSTRACT

OBJECTIVE: Some studies have highlighted psychological and neuropsychological difficulties and a potential reduction in health-related quality of life (HRQOL) in patients with pituitary tumors, despite hormone deficits or excess. To the authors' knowledge, this study is the first prospective longitudinal case-control study with the aim of simultaneously testing whether HRQOL and psychiatric and neuropsychological disabilities are related to neural dysfunction due to hypercortisolism per se, or tumor mass and/or surgery in patients with Cushing's disease (CD). The authors evaluated a homogeneous cohort of patients with CD and nonfunctioning pituitary adenomas (NFPAs) before and after neurosurgery and compared these patients with healthy controls. METHODS: Twenty patients (10 with NFPA and 10 with CD) were evaluated using 3 validated questionnaires (SF-36, Beck Depression Inventory-II [BDI-II], and Minnesota Multiphasic Personality Inventory-II [MMPI-II]) to assess HRQOL and psychological status preoperatively and 12 months after neurosurgery. Neuropsychological tests were assessed preoperatively, 3-7 days postoperatively, and 12 months postoperatively. Twenty healthy matched controls were recruited. RESULTS: Preoperatively, the NFPA and CD subgroups had worse HRQOL scores than controls on the basis of SF-36 scores, although the NFPA subgroup experienced significant recovery 12 months postoperatively. Preoperatively, CD patients had depressive symptoms according to the BDI-II and MMPI-II that persisted 12 months postoperatively, together with social introversion and hypochondriasis; NFPA patients were similar to controls except for hypochondriasis scores that were clinically significant at all timepoints. Preoperatively and 3-7 days postoperatively, both subgroups showed significant neuropsychological disabilities compared with controls, but only the CD subgroup did not completely recover over time. CONCLUSIONS: HRQOL and neuropsychological impairments were observed in all patients at early timepoints, independent of hypercortisolism, tumor mass, and successful surgery. Over time, CD patients showed persistent changes in HRQOL, in particular in social activities. In this light, CD seems to have a strong impact on HRQOL and to be associated with more psychological and neuropsychological comorbidities than NFPA.

13.
Neurosurg Focus ; 47(4): E12, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31574466

ABSTRACT

OBJECTIVE: Recent trials have shown the safety and benefits of fetoscopic treatment of myelomeningocele (MMC). The authors' aim was to report their preliminary results of prenatal fetoscopic treatment of MMC using a biocellulose patch, focusing on neurological outcomes, fetal and maternal complications, neonatal CSF leakage, postnatal hydrocephalus, and radiological outcomes. METHODS: Preoperative assessment included clinical examination, ultrasound imaging, and MRI of the fetus. Patients underwent purely fetoscopic in utero MMC repair, followed by postoperative in utero and postnatal MRI. All participants received multidisciplinary follow-up. RESULTS: Five pregnant women carrying fetuses affected by MMC signed informed consent for the fetoscopic treatment of the defect. The mean MMC size was 30.4 mm (range 19-49 mm). Defect locations were L1 (2 cases), L5 (2 cases), and L4 (1 case). Hindbrain herniation and ventriculomegaly were documented in all cases. The mean gestational age at surgery was 28.2 weeks (range 27.8-28.8 weeks). Fetoscopic repair was performed in all cases. The mean gestational age at delivery was 33.9 weeks (range 29.3-37.4 weeks). After surgery, reversal of hindbrain herniation was documented in all cases. Three newborns developed signs of hydrocephalus requiring CSF diversion. Neurological outcomes in terms of motor level were favorable in all cases, but a premature newborn died due to CSF infection and sepsis. CONCLUSIONS: The authors' preliminary results suggest that fetoscopic treatment of MMC is feasible, reproducible, and safe for mothers and their babies. Neurological outcomes were favorable and similar to those in the available literature. As known, prematurity was the greatest complication.


Subject(s)
Hydrocephalus/surgery , Meningomyelocele/surgery , Minimally Invasive Surgical Procedures , Adult , Female , Fetoscopy/methods , Gestational Age , Humans , Infant, Newborn , Minimally Invasive Surgical Procedures/methods , Pregnancy , Treatment Outcome
14.
J Alzheimers Dis ; 69(3): 663-669, 2019.
Article in English | MEDLINE | ID: mdl-31156164

ABSTRACT

Aquaporin4 (AQP4) is a water channel protein located at astrocyte foot processes that plays a role in glymphatic system, a highly organized fluid transport pathway which seems to be involved in Alzheimer's disease (AD) and normal pressure hydrocephalus (NPH) pathophysiology. Cerebrospinal fluid (CSF) AQP4 levels were determined in 11 patients with AD, 10 patients with NPH, and 9 controls. We found significantly reduced AQP4 in AD patients, a trend in reduction in NPH patients, and a correlation between AQP4 and amyloid-ß CSF levels. This study indicates the potential role of AQP4 and glymphatic system in neurodegenerative diseases pathophysiology.


Subject(s)
Aquaporin 4/cerebrospinal fluid , Glymphatic System/metabolism , Neurodegenerative Diseases/cerebrospinal fluid , Neurodegenerative Diseases/metabolism , Aged , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/cerebrospinal fluid , Female , Glymphatic System/physiopathology , Humans , Hydrocephalus, Normal Pressure/cerebrospinal fluid , Male , Neurodegenerative Diseases/physiopathology , tau Proteins/cerebrospinal fluid
15.
Stem Cells Int ; 2019: 2617030, 2019.
Article in English | MEDLINE | ID: mdl-30984267

ABSTRACT

Glioblastoma (GBM) is the most malignant human brain tumour, characterized by rapid progression, invasion, intense angiogenesis, high genomic instability, and resistance to therapies. Despite countless experimental researches for new therapeutic strategies and promising clinical trials, the prognosis remains extremely poor, with a mean survival of less than 14 months. GBM aggressive behaviour is due to a subpopulation of tumourigenic stem-like cells, GBM stem cells (GSCs), which hierarchically drive onset, proliferation, and tumour recurrence. The morbidity and mortality of this disease strongly encourage exploring genetic characteristics of GSCs. Here, using array-CGH platform, we investigated genetic and genomic aberration profiles of GBM parent tumour (n = 10) and their primarily derived GSCs. Statistical analysis was performed by using R software and complex heatmap and corrplot packages. Pearson correlation and K-means algorithm were exploited to compare genetic alterations and to group similar genetic profiles in matched pairs of GBM and derived GSCs. We identified, in both GBM and matched GSCs, recurrent copy number alterations, as chromosome 7 polysomy, chromosome 10 monosomy, and chromosome 9p21deletions, which are typical features of primary GBM, essential for gliomagenesis. These observations suggest a condition of strong genomic instability both in GBM as GSCs. Our findings showed the robust similarity between GBM mass and GSCs (Pearson corr.≥0.65) but also highlighted a marked variability among different patients. Indeed, the heatmap reporting Gain/Loss State for 21022 coding/noncoding genes demonstrated high interpatient divergence. Furthermore, K-means algorithm identified an impairment of pathways related to the development and progression of cancer, such as angiogenesis, as well as pathways related to the immune system regulation, such as T cell activation. Our data confirmed the preservation of the genomic landscape from tumour tissue to GSCs, supporting the relevance of this cellular model to test in vitro new target therapies for GBM.

18.
World Neurosurg ; 122: e226-e234, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30312827

ABSTRACT

BACKGROUND: Angiogenesis has been shown to be strictly related to tumor malignancy. Glioblastoma (GBM) is highly vascularized and von Willebrand Factor (VWF) plays a potent proangiogenic role. Dynamic contrast-enhanced and dynamic susceptibility contrast magnetic resonance imaging (MRI) represent a widely accepted method to assess GBM microvasculature. Our aim was to investigate the correlation between plasma VWF:Ag, permeability, and perfusion MRI parameters and examine their potential in predicting GBM patient prognosis. METHODS: We retrospectively analyzed preoperative dynamic contrast-enhanced, dynamic susceptibility contrast MRI, and VWF:Ag level of 26 patients with GBM. We assessed the maximum values of relative cerebral blood flow and volume, volume transfer constant Ktrans, plasma volume (Vp) and reflux rate constant between fractional volume of the extravascular space and blood plasma (Kep). Nonparametric Mann-Whitney test and Kaplan-Meier survival analyses were conducted and a P value < 0.05 was considered statistically significant. RESULTS: The median VWF:Ag value was 248 IU/dL and the median follow-up duration was about 13 months. We divided patients according to low-VWF:Ag and high-VWF:Ag and we found significant differences in the median follow-up duration (19 months vs. 10 months; P = 0.04) and in Ktrans (0.31/minute vs. 0.53/minute; P = 0.02), and Kep (1.79/minute vs. 3.89/minute; P = 0.005) values. The cumulative 1-year survival was significantly shorter in patients with high-VWF:Ag and high-Kep compared with patients with low-VWF:Ag and low-Kep (37.5% vs. 68%; P = 0.05). CONCLUSIONS: These findings, in a small group of patients, suggest a role for VWF:Ag, similar to Ktrans, and Kep as a prognostic indicator of postoperative survival of patients with GBM.


Subject(s)
Brain Neoplasms/diagnosis , Glioblastoma/diagnosis , Magnetic Resonance Angiography , von Willebrand Factor/metabolism , Aged , Biomarkers/blood , Blood Volume , Brain/diagnostic imaging , Cerebrovascular Circulation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
19.
World Neurosurg ; 121: e621-e629, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30292037

ABSTRACT

BACKGROUND: Coagulation is an important aspect of the vascular microenvironment in which brain tumors evolve. Patients with tumor often show aberrant coagulation and fibrinolysis activation. In particular, glioblastoma (GBM), the most aggressive primary brain tumor, is associated with a state of hypercoagulability, and venous thromboembolism is a common complication of this cancer and its treatment. Our study aims to investigate the clinical and prognostic significance of routine laboratory tests to assess the coagulative state of patients with brain tumors, to identify potential new prognostic factors and targets for personalized therapy. METHODS: Blood samples were collected from patients with GBM (n = 58) and patients with meningioma (MNG, n = 22), before any treatment. The parameters analyzed were prothrombin time (PT), activated partial thromboplastin time (aPTT), D dimer (DD), fibrinogen, von Willebrand factor (VWF), leukocyte count, and hemoglobin levels. RESULTS: Plasma levels of PT and aPTT were significantly reduced in GBMs compared with MNGs (P < 0.05), whereas DD, VWF:Ag levels, and leukocyte count were significantly higher in GBMs than in MNGs (P < 0.01). Furthermore, we observed that patients with GBM with reduced PT and aPTT and high levels of DD and VWF, defined as hypercoagulable patients, showed reduced overall survival (P < 0.05) compared with nonhypercoagulable patients. CONCLUSIONS: Our data support the assumption that patients with GBM show a plasma hypercoagulable profile and that coagulation profile is related to adverse outcome in patients with GBM. If confirmed, hypercoagulability could play an important role as a prognostic factor of the disease and in the decision of an antithrombotic prophylaxis.


Subject(s)
Brain Neoplasms/blood , Brain Neoplasms/diagnosis , Glioblastoma/blood , Glioblastoma/diagnosis , Partial Thromboplastin Time/methods , Aged , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Hemoglobins/metabolism , Humans , Kaplan-Meier Estimate , Leukocyte Count , Male , Meningeal Neoplasms/blood , Meningeal Neoplasms/diagnosis , Meningioma/blood , Meningioma/diagnosis , Middle Aged , Prognosis , von Willebrand Factor/metabolism
20.
J Neurosurg Sci ; 63(1): 30-35, 2019 Feb.
Article in English | MEDLINE | ID: mdl-27387147

ABSTRACT

BACKGROUND: Does posterior cervical herniectomy impact on symptoms related to cervical paramedian/lateral soft disc herniation? METHODS: In a patient series over 15 years operated for single level paramedian/lateral soft disc herniation with posterior cervical approach, perceived radicular and cervical pre- and postoperative symptoms were reconstructed and analyzed. RESULTS: Out of 105 patients with these characteristics 75 could be recruited for long-term follow-up. Preoperative symptoms included: radicular motor deficit (81.3%); radicular pain (93.3%); radicular sensory deficit (84%); cervical pain (80%) and disturbance of cervical motility (49.3%). Postoperatively radicular motor score improved in all patients (score 5 in 92% and 4 in 8%); sensory disturbance improved in all and radicular pain disappeared in 90% and improved in the others. Cervical pain disappeared in 78% and improved in other 22%, two had new onset moderate cervical pain. CONCLUSIONS: This series confirms safety and efficacy of the posterior approach in relieving motor and sensory symptoms in patients with symptomatic single level, lateral soft disc herniation.


Subject(s)
Decompression, Surgical/methods , Diskectomy/methods , Intervertebral Disc Displacement/surgery , Outcome and Process Assessment, Health Care , Pain/surgery , Adult , Decompression, Surgical/adverse effects , Diskectomy/adverse effects , Female , Follow-Up Studies , Humans , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/physiopathology , Male , Middle Aged , Pain/etiology
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