Interplay between speech and gait variables in Parkinson's disease patients treated with subthalamic nucleus deep brain stimulation: A long-term instrumental assessment.

OBJECTIVE: To evaluate correlations between speech and gait parameters in the long term and under different medication and subthalamic nucleus deep brain stimulation (STN-DBS) conditions in a cohort of advanced Parkinson's disease (PD) patients. METHODS: This observational study included consecutive PD patients treated with bilateral STN-DBS. Axial symptoms were evaluated using a standardized clinical-instrumental approach. Speech and gait were assessed by perceptual and acoustic analyses and by the instrumented Timed Up and Go (iTUG) test, respectively. Disease motor severity was evaluated with the total score and subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Different stimulation and drug treatment conditions were assessed: on-stimulation/off-medication, off-stimulation/off-medication, and on-stimulation/on-medication. RESULTS: Twenty-five PD patients with a 5-year median follow-up after surgery (range 3-7 years) were included (18 males; disease duration at surgery: 10.44 [SD 4.62] years; age at surgery: 58.40 [SD 5.73] years). In the off-stimulation/off-medication and on-stimulation/on-medication conditions, patients who spoke louder had also the greater acceleration of the trunk during gait; whereas in the on-stimulation/on-medication condition only, patients with the poorer voice quality were also the worst to perform the sit to stand and gait phases of the iTUG. Conversely, patients with the higher speech rate performed well in the turning and walking phases of the iTUG. CONCLUSIONS: This study underlines the presence of different correlations between treatment effects of speech and gait parameters in PD patients treated with bilateral STN-DBS. This may allow us to better understand the common pathophysiological basis of these alterations and to develop a more specific and tailored rehabilitation approach for axial signs after surgery.

Hemorrhagic Stroke: Endoscopic Aspiration.

Intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) carry a very dismal prognosis. Several medical and surgical attempts have been made to reduce mortality and to improve neurological outcomes in survivors. Aggressive surgical treatment of ICH through craniotomy and microsurgical evacuation did not prove to be beneficial to these patients, compared to the best medical treatment. Similarly, the conventional treatment of IVH using an EVD is often effective in controlling ICP only initially, as it is very likely for the EVD to become obstructed by blood clots, requiring frequent replacements with a consequent increase of infection rates.Minimally invasive techniques have been proposed to manage these cases. Some are based on fibrinolytic agents that are infused in the hemorrhagic site through catheters with a single burr hole. Others are possible thanks to the development of neuroendoscopy. Endoscopic removal of ICH through a mini-craniotomy or a single burr hole, and via a parafascicular white matter trajectory, proved to reduce mortality in this population, and further randomized trials are expected to show whether also a better neurological outcome can be obtained in survivors. Moreover, endoscopy offers the opportunity to access the ventricular system to aspirate blood clots in patients with IVH. In such cases, the restoration of patency of the entire CSF pathway has the potential to improve outcome and reduce complications and now it is believed to decrease shunt-dependency.

Spinal hemangioblastomas: analysis of surgical outcome and prognostic factors.

The prognostic factors for surgically removed spinal hemangioblastomas, the impact of VHL disease on outcome, and the role of intraoperative neuromonitoring are still not completely clear. The aim of this study was to review our experience with spinal hemangioblastomas in order to assess potential predictors of neurological outcome after surgery. All cases of spinal hemangioblastomas removed at two Italian academic institutions from 1985 to 2020 were reviewed. Data about clinical presentation and symptom duration, diagnosis of VHL, surgical approach, use of IONM, duration of hospital stay, follow-up, and modified McCormick grade before and after surgery were extracted. Sixty-one patients (31 F, 30 M) underwent 69 surgeries to remove 74 spinal hemangioblastomas (37 cervical, 32 thoracic, 5 lumbar). Improvement was found in 32.3% of cases, neurological condition remained stable in 51.6% of cases, and deteriorated in 16.1% of patients. A worsening trend in VHL patients and an improvement trend in non-VHL patients were detected, despite the lack of statistical significance. Laminotomy and use of IONM were found to be associated with better outcome, although no association was found between surgery without IONM and worse outcome. In most cases, patients affected by spinal hemangioblastomas can expect a good long-term outcome. In our experience, laminotomy seems to be associated with better outcome compared to laminectomy. While its absence is not associated with worse outcome, IONM seems to be associated with a better neurological outcome. Our study suggests that the more impaired the preoperative neurological condition, the worse the outcome.

Efficacy and safety of flexible versus rigid endoscopic third ventriculostomy in pediatric and adult populations: a systematic review and meta-analysis.

Endoscopic third ventriculostomy (ETV) is a well-established surgical procedure for hydrocephalus treatment, but there is sparse evidence on the optimal choice between flexible and rigid approaches. A meta-analysis was conducted to compare efficacy and safety profiles of both techniques in pediatrics and adults. A comprehensive search was conducted on PubMED, EMBASE, and Cochrane until 11/10/2019. Efficacy was evaluated comparing incidence of ETV failure, while safety was defined by the incidence of perioperative complications, intraoperative bleedings, and deaths. Random-effects models were used to pool the incidence. Out of 1365 studies, 46 case series were meta-analyzed, yielding 821 patients who underwent flexible ETV and 2918 who underwent rigid ETV, with an age range of [5 days-87 years]. Although flexible ETV had a higher incidence of failure in adults (flexible: 54%, 95%CI: 22-82% vs rigid: 20%, 95%CI: 22-82%) possibly due to confounding due to etiology in adults treated with flexible, a smaller difference was seen in pediatrics (flexible: 36%, pediatric: 32%). Safety profiles were acceptable for both techniques, with a certain degree of variability for complications (flexible 2%, rigid 18%) and death (flexible 1%, rigid 3%) in pediatrics as well as complications (rigid 9%, flexible 13%), death (flexible 4%, rigid 6%) and intra-operative bleeding events (rigid 6%, flexible 8%) in adults. No clear superiority in efficacy could be depicted between flexible and rigid ETV for hydrocephalus treatment. Safety profiles varied by age but were acceptable for both techniques. Well-designed comparative studies are needed to assess the optimal endoscopic treatment option for hydrocephalus.

How I do it: flexible endoscopic aspiration of intraventricular hemorrhage.

BACKGROUND: As intraventricular blood is a strong negative prognostic factor, intraventricular hemorrhage requires prompt and aggressive management to reduce intracranial hypertension. METHOD: A flexible scope can be used to navigate and to aspirate blood clots from all four ventricles. Complete restoration of CSF pathways from the lateral ventricle to the foramen of Magendie can be obtained. CONCLUSION: Flexible neuroendoscopic aspiration of IVH offers the opportunity to immediately reduce intracranial hypertension, reduce EVD obstruction and replacement rates, and decrease infections and shunt dependency.

Myelomeningocele Repair Combining a Double Cryopreserved Amniotic Membrane Homograft and the Keystone Flap in a 3-Year-Old Child: A Case Report.

INTRODUCTION: Early repair in patients affected by myelomeningocele (MMC) is of paramount importance in order to prevent infection, minimize neural tissue damage, and reduce mortality. Treatment must include duraplasty and possibly an adequate soft tissue coverage. Delayed surgery in MMC patients can be more tedious due to the less clear borders between the placode and the skin. Moreover, the risks of wound infection and breakdown increase significantly. CASE PRESENTATION: We present the unusual case of a large MMC in a 3-year-old patient treated by combining the recently described cryopreserved amniotic membrane (AM) as homograft for dural reconstruction and a bilateral Keystone flap for soft tissue reconstruction. DISCUSSION: Thanks to its anti-inflammatory and elastic proprieties, the AM can play an important role in preventing adhesion between the reconstructed layers, thus reducing the risk of spinal cord tethering. The Keystone flap, at the same time, allows the wound tension to be distributed widely over the flap margins and not only along the midline, which overlies the duraplasty, enhancing the scar quality and lowering the risk of cerebrospinal fluid recurrence and wound dehiscence, with no donor site morbidity.

High speed flow cytometry allows the detection of circulating endothelial cells in hemangioblastoma patients.

Circulating endothelial cells (CECs) detach from the intima monolayer after endothelial damages. Their circulating endothelial progenitors (CEPs) represent less than 0.01% of nucleated blood cells. Increased levels of CECs and CEPs have been detected in patients with several types of cancer, suggesting that they could be a useful blood-based marker for detecting a tumor, or for monitoring its clinical course. However, their routine monitoring is time consuming and technically challenging. Here, we present a flow cytometry method for quantifying such cells in a cohort of patients with hemangioblastoma (HB). HB is a rare benign tumor, responsible for 1-2.5% of primary intracranial tumors and up to 10% of spinal cord tumors, and for which no tools are available to predict the onset or recurrence in patients undergoing surgical removal of tumor mass. This method allowed us to accurately quantifying CEC and CEP before and after surgery. CEPs are present at high levels in HB patients than control before intervention, and decrease after tumor removal, suggesting that their percentage could represent a valid tool to monitor the disease onset and recurrence.

Computational Fluid Dynamics Analysis and Correlation with Intraoperative Aneurysm Features.

INTRODUCTION: There are many controversies about computational fluid dynamics (CFD) findings and aneurysm initiation, growth, and ultimate rupture. The aim of our work was to analyze CFD data in a consecutive series of patients and to correlate them with intraoperative visual aneurysm findings. METHODS: Hemoscope software (Amin, Ziosoft Corporation, Minato ward, Tokyo, Japan) was used to process images from 17 patients who underwent clipping of 18 aneurysms. Pressure (P), wall shear stress (WSS) gradient and vectors, normalized WSS, and streamlines (SL) direction and velocity were assessed. CFD data were compared to intraoperative visual findings. A total of 39 aneurysm wall areas were assessed. RESULTS: Red, thin aneurysm wall areas were more often associated with low WSS. However, the association of low WSS with high P, diverging WSS vectors, direct impact of SL, and high SL velocity more frequently matched with yellow, atherosclerotic aneurysm walls. CONCLUSIONS: Low WSS alone is not sufficient to determine the thickness of an aneurysm wall. Its association with other parameters might enable one to distinguish preoperatively atherosclerotic, thick areas (high P, diverging WSS vectors, high flow velocity) from thin areas with higher rupture risk (parallel WSS vectors, lower flow velocity). The changing balance between these parameters can modify the features and the risk of rupture of aneurysm wall over time.

Split cerebral aqueduct: a neuroendoscopic illustration.

PURPOSE: Forking of the cerebral aqueduct is a developmental malformation that is infrequently encountered by neurosurgeons as a rare cause of hydrocephalus, sometimes with a delayed onset. The etiology of an apparently forked aqueduct might be different. However, neuroendoscopy can often be the optimal treatment. The purpose of this study was to review the literature by analyzing the anatomical, functional, diagnostic, and therapeutic features of this unusual condition and adding our personal cases. METHODS: We present a case of forking of the cerebral aqueduct that was detected in vivo and treated with a flexible scope. A thorough review of the pertinent literature is also discussed. In the past years, diagnosis of forked aqueduct was possible only postmortem. RESULTS: A forked aqueduct is occasionally encountered in patients when a delayed hydrocephalic decompensation occurs. CONCLUSIONS: Flexible neuroendoscopy enables for a direct, in vivo diagnosis and immediate treatment through a third ventriculostomy.

Aspiration of parafalcine empyemas with flexible scope.

PURPOSE: Subdural empyemas are considered neurosurgical emergencies, and the parafalcine location is particularly insidious. We revised the experience of general surgeons who are used to manage chronic pleural purulent collections with video-assisted thoracoscopy. METHODS: With a similar technique, we successfully aspirated a parafalcine empyema using a flexible scope avoiding a more invasive craniotomy. A review of the treatment options of empyematous collections is also provided, focusing particularly on the hazardous parafalcine location. RESULTS: The management of subdural empyemas poses different decision-making problems compared to common brain abscesses, urging a more rapid and holistic surgical treatment with minimally invasive approach. Endoscopic aspiration of parafalcine empyema was followed by complete recovery in our patient. CONCLUSIONS: Flexible endoscopy is a promising method to obtain complete pus removal even from loculated collections through a bur hole, avoiding large craniotomies and consequent potential complications.

Transaqueductal trans-Magendie fenestration of arachnoid cyst in the posterior fossa.

BACKGROUND: Neuroendoscopy is currently recommended as the first choice to treat posterior fossa arachnoid cysts. It has proven to be effective, providing improved outcome, and safe, having a low complication rate. Compared to craniotomy and shunt placement, it has lower surgical morbidity, minimizing or avoiding risks of subdural fluid collections, shunt infection, malfunction, overdrainage, and dependence. Usually, rigid scopes maneuvered through a suboccipital approach are used. When symptomatic obstructive hydrocephalus develops, CSF diversion is the first aim of surgery. METHODS: In these patients, a flexible scope introduced through a frontal burr hole allows not only immediate and efficient management of hydrocephalus with endoscopic third-ventriculostomy, but in selected cases also direct cyst inspection and fenestration. Navigation of an enlarged cerebral aqueduct is actually safe when performed by experienced neurosurgeons. RESULTS: We describe the cystocisternostomy of a cisterna magna arachnoid cyst using a transaqueductal trans-Magendie approach. CONCLUSIONS: This minimally invasive technique gives the possibility of performing both endoscopic third-ventriculostomy and cyst fenestration, which alone may not be enough to efficiently treat hydrocephalus.

Carbon dioxide field flooding reduces the hemodynamic effects of venous air embolism occurring in the sitting position.

PURPOSE: Although the utility of the sitting position is undisputed for biomechanical and ergonomic reasons, it has been debated in recent years for its risks, particularly venous air embolism (VAE). In order to reduce the hemodynamic effect of VAE, we changed the composition of the surgical field air partially replacing nitrogen with carbon dioxide (CO2) that better dissolves in human tissues. METHODS: First, we tested our method on a test dummy in the sitting position. Infrared CO2 sensors were placed close to the wound opening and on the facial mask of the surgeon. An oxygen sensor was connected to a computer for data recording (ALTAIR(®), MSA Safety). This model showed that 10 L/min CO2 flow provides efficient air displacement, maintaining safety for the surgeon. We reproduced the above-described surgical field environment in ten consecutive cases of posterior fossa surgery performed in the sitting position. A homogeneous group of ten patients operated in the sitting position with standard setting environment was used for control. We intraoperatively monitored VAE with trans-esophageal echocardiography (TEE), end-tidal CO2 (ETCO2), CO2 arterial pressure (PaCO2), and hemodynamic changes. RESULTS: Although the percentage of VAE was 70% in both groups, hemodynamic effects occurred in 10% of cases in the study group and in 40% of cases in the control group. CONCLUSIONS: Our preliminary study shows that a CO2-enriched sitting position surgical microenvironment significantly reduces the hemodynamic effects of VAE, more likely because arterial CO2 emboli are more soluble and consequently much better tolerated than air emboli.

The Cerebral Aqueduct Compliance: A Simple Morphometric Model.

BACKGROUND AND OBJECTIVES: This work aimed to identify different configurations of the adytum of the cerebral aqueduct suggesting its safe neuroendoscopic navigation. This concept is intimately connected to the physiological aqueductal dilatability or compliance, which is relatively ignored in the literature. A better knowledge of the extent of physiological aqueductal dilatability might better define the ideal diameter and safer features of dedicated flexible endoscopes. METHODS: The study includes 45 patients operated on using a flexible scope with a 3.9-mm diameter, where the structural elements of the adytum of the cerebral aqueduct are clearly visible. Patients were grouped according to the pathology (colloid cyst/normal anatomy, intraventricular hemorrhage, tetraventricular obstructive hydrocephalus, normal pressure hydrocephalus, and distal membranous aqueductal stenosis). A simple geometrical scheme was applied to the endoscopic anatomy of the aqueductal adytum in relation to the posterior commissure to measure its pathologic deformations. Eventual damages to the aqueduct walls caused by the endoscope were also reported. RESULTS: Proceeding from normal anatomy to hydrocephalic condition, the ratio between the commissure and the aqueductal access area progressively decreases, while the vertex angle increases. Interestingly, the entity of the ependymal damages due to the passage of the endoscope correlates with such measures. CONCLUSION: The cerebral aqueduct, excluding atrophic processes, is provided with a certain degree of dilatability, which we estimate to be around a diameter of 4 mm. This represents the maximum size for a flexible neuroendoscope for a safe aqueductal neuronavigation. The schematic model of the aqueductal adytum as a triangle defines 3 different aqueductal patterns and can be helpful when an intraoperative decision on whether to navigate the aqueduct must be taken.

H3 K27M mutation in rosette-forming glioneuronal tumors: a potential diagnostic pitfall.

According to the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS), diffuse midline glioma H3 K27-altered is a grade 4 infiltrative glioma that arises from midline anatomical structures and is characterized by the loss of H3 K27me3 and co-occurring H3 K27M mutation or EZHIP overexpression. However, the H3 K27M mutation has also been observed in circumscribed gliomas and glioneuronal tumors arising in midline anatomical structures, which may result in diagnostic pitfalls.Rosette-forming glioneuronal tumor (RGNT) is a CNS WHO grade 1 neoplasm that histologically features neurocytic and glial components and originates in midline anatomical structures.This study aimed to assess whether RGNTs, similar to other midline tumors, may exhibit immunohistochemical loss of H3 K27me3 and harbor the H3 K27M mutation.All seven analyzed RGNTs displayed immunohistochemical loss of H3 K27me3 in all tumor cells or H3 K27me3 mosaic immunostaining. In one case, H3 K27me3 loss was associated with the H3 K27M mutation, whereas the other six cases did not exhibit any H3 mutations or EZHIP overexpression. During a follow-up period of 23 months, the H3 K27M-mutant case remained unchanged in size despite partial resection, indicating that the H3 mutation may not confer higher biological aggressiveness to RGNT.The immunohistochemical loss of H3 K27me3 co-occurring with the H3 K27M mutation may result in the potential misdiagnosis of RGNT, especially in cases of small biopsy specimens consisting of only the glial component.

Decoding the puzzle: A multidisciplinary systematic review of adult brainstem glioma.

Adult brainstem gliomas (BSGs) are a group of rare central nervous system tumors with varying prognoses and controversial standard treatment strategies. To provide an overview of current trends, a systematic review using the PRISMA guidelines, Class of evidence (CE) and strength of recommendation (SR), was conducted. The review identified 27 studies. Surgery was found to have a positive impact on survival, particularly for focal lesions with CE II SR C. Stereotactic image-guided biopsy was recommended when resective surgery was not feasible with CE II and SR B. The role of systemic treatments remains unclear. Eight studies provided molecular biology data. This review gathers crucial literature on diagnosis and management of adult BSGs. It provides evidence-based guidance with updated recommendations for diagnosing and treating, taking into account recent molecular and genetic advancements. The importance of brain biopsy is emphasized to optimize treatment using emerging genetic-molecular findings and explore potential targeted therapies.

Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma.

Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients.

Hemorrhage Volume Drives Early Brain Injury and Outcome in Poor-Grade Aneurysmal SAH.

BACKGROUND AND PURPOSE: Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV-V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome. MATERIALS AND METHODS: Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3-4), in-hospital mortality (mRS 6), and functional independence (mRS 0-2) at follow-up. RESULTS: Among 400 patients (median global intracranial hemorrhage volume of 91 mL; interquartile range, 59-128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0-2 at a median of 13 (interquartile range, 3-26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004-1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001-1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98-0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50-70, older than 70 year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome. CONCLUSIONS: Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema.

Gliomas of the pineal region.

Although several series of pineal region tumors are available, the issue of pineal gliomas has been scarcely faced in the literature. Gliomas are usually included in largest series of pineal neoplasms. Therefore, whether pineal gliomas share the biological behavior of either hemispheric gliomas or other midline lesions is not yet defined. The aim of this retrospective study is to analyze long-term morbidity and mortality of these lesions. In English published literature gliomas account for about 14-22 % of all pineal region tumors. Most of these tumors are pilocytic astrocytomas, while glioblastoma multiforme is rare. We retrospectively analyzed all pineal region tumors operated on in our department in the last 28 years, and identified eight pineal astrocytomas, accounting for 14.03 % of all pineal tumors. The series includes four pilocytic astrocytomas, two grade II diffuse astrocytomas, and two anaplastic astrocytomas. A comprehensive review of the available literature data shows that the mean survival time of WHO grade II gliomas is shorter when tumor grows in the pineal region than for hemispheric locations, although the limited amount of available data prevents a rigorous statistical analysis. This difference might be due to the peculiar infiltrating behavior of pineal tumors, which often can't be satisfactorily resected from vital structures.