Middle Meningeal Artery Embolization Minimizes Burdensome Recurrence Rates After Newly Diagnosed Chronic Subdural Hematoma Evacuation (MEMBRANE): study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural hematoma (cSDH) is the most common complication of mild traumatic brain injury demanding neurosurgery in high-income countries. If undetected and untreated, cSDH may increase intracranial pressure and cause neurological deficiencies. The first-line intervention of choice is burr hole trepanation and hematoma evacuation. However, any third patient may experience rebleeding, demanding craniotomy with excess morbidity. Adjunct endovascular embolization of the frontal and parietal branches of the middle meningeal artery (MMA) is a promising approach to avoid relapse and revision but was hitherto not studied in a randomized trial. METHODS: MEMBRANE is an investigator-initiated, single-center, randomized controlled trial. Male, female, and diverse patients older than 18 years scheduled for surgical evacuation of a first cSDH will be assigned in a 1:1 fashion by block randomization to the intervention (surgery plus endovascular MMA embolization) or the control group (surgery alone). The primary trial endpoint is cSDH recurrence within 3 months of follow-up after surgery. Secondary endpoints comprise neurological deficits assessed by the modified Rankin Scale (mRS) and recurrence- or intervention-associated complications during 3 months of follow-up. Assuming a risk difference of 20% of rebleeding and surgical revision, a power of 80%, and a drop-out rate of 10%, 154 patients will be enrolled onto this trial, employing an adaptive O'Brien-Fleming approach with a planned interim analysis halfway. DISCUSSION: The MEMBRANE trial will provide first clinical experimental evidence on the effectiveness of endovascular embolization of the MMA as an adjunct to surgery to reduce the risk of recurrence after the evacuation of cSDH. TRIAL REGISTRATION: German Clinical Trials Registry (Deutsches Register Klinischer Studien [DRKS]) DRKS00020465. Registered on 18 Nov 2021. CLINICALTRIALS: gov NCT05327933 . Registered on 13 Apr 2022.

The role of shuntography in diagnosis of mechanic complications after implantation of ventriculoperitoneal shunts in patients with idiopathic normal pressure hydrocephalus: a retrospective clinical evaluation.

BACKGROUND: Mechanical obstruction of ventriculoperitoneal shunt (VPS) during the first year after shunt implantation is a common complication and is widely described in the literature. In this paper, we evaluated the suitability of the shuntography for the diagnosis of mechanical complications of the VPS in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: We retrospectively identified 49 patients with pathologic shuntography over of a period of 20 years in our hospital. The percentage of procedure-associated complications was determined. RESULTS: Ninety-eight percent (n = 48) of the patients who underwent shuntography showed clinical and radiographic signs of underdrainage prior to examination. Shuntography revealed mechanical complications of the VP shunt in 37% (n = 18) as a cause of clinical deterioration and following revision operation. During shuntography, mechanical obstruction was discovered in 78% (n = 14) and disconnection of shunt components in 22% (n = 4). In the obstruction group, in 50% (n = 7) the closure was detected in the ventricular catheter, in 29% (n = 4) in the distal catheter of the VPS, and in 21% (n = 3) in both sides of the VPS. In the case of an inconspicuous shuntography (63%, n = 31), the patients received symptomatic therapy (32%, n = 10) or re-adjustment of the valve setting (68%, n = 21). Fifty-seven percent of the patients who underwent surgical treatment improved clinically by at least one point according to the Kiefer score. CONCLUSION: Shuntography can produce valuable clinical information uncovering mechanic complications after implantation VPS in patients with idiopathic normal-pressure hydrocephalus. Patients with mechanical complications of their VPS needed revision surgery and showed clinical benefit after treatment.

Step Back in Order to Go Forward: Willful Enlargement and Sandwich Closure Technique for Spinal Dura Repair after Several Unsuccessful Closure Attempts.

A CSF leak is a common complication in spine surgery which is usually closed effectivly by suture and/or epidural patches. There is currently no algorithm to treat a recurrent CSF leak that fails to be closed initially. We describe the case of a recurrent cerebrospinal fluid leak that we have successfully treated using an inlay-onlay dural repair technique.

Gravitational shunt valves in hydrocephalus to challenge the sequelae of over-drainage.

INTRODUCTION: In hydrocephalus treatment, ventriculo-peritoneal shunts (VPS) have become the most relevant therapy for seven decades among other treatment options. Due to the hydrostatic pressure in vertical position, CSF diversion is somehow non-physiological. The integration of gravitational valves in VPS was established to counteract the hydrostatic draining force and to approach a physiological condition of the cerebrospinal diverting system. Numerous clinical studies have shown that gravitational valves are able to reduce secondary complications of VPS treatment. It remains a challenge for the treating neurosurgeon to select the correct valve resistance based on individual anatomies and different etiologies of hydrocephalus as well as varying levels of activity of the patient. AREAS COVERED: This review covers the development of gravitational shunt valves from historical, theoretical and clinical aspects for pediatric and adult etiologies of hydrocephalus. We discuss the role of gravitational shunt valves in preventing over-drainage issues and present the state-of-the-art literature. Furthermore, ongoing prospective trials are presented. EXPERT OPINION: Counteracting the hydrostatic force by selecting the correct valve in a VPS system to achieve physiological balance in CSF diversion during vertical and horizontal body changes has become the current standard for hydrocephalus management. Gravitational shunt valves reliably address this need to minimize over-drainage events in the vertical position without affecting the CSF flow in the horizontal position. The results of ongoing prospective studies on the safety and efficacy of adjustable gravitational valves are still pending. Due to the complexity of the CSF flow, lifelong follow-up care for patients with VPS is critical.

Secondary deterioration in patients with normal pressure hydrocephalus after ventriculoperitoneal shunt placement: a proposed algorithm of treatment.

BACKGROUND: After ventriculoperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (iNPH) with adjustable gravitational valves, a certain proportion of patients develop secondary clinical worsening after initial improvement of clinical symptoms. The aim of this study was to analyze this group of patients with secondary deterioration and to evaluate the performed shunt management. METHODS: For this investigation, we retrospectively reviewed our NPH registry for patients included between 1999 and 2013 with a decrease by a minimum of two points in the Kiefer score in the first year of follow up and an increase of two points in the Kiefer score between the second and the fifth year after shunt surgery (secondary deterioration). Then, we analyzed the patient's shunt management (adapting the valve pressure setting, shuntography, valve replacement, catheter replacement, implant an adjustable gravitational unit). Additionally, we searched for risk factors for secondary deterioration. RESULTS: Out of 259 iNPH patients, 53 (20%) patients showed secondary deterioration on an average of 2.7 (2-4 years) years after shunt surgery. Fourteen (26%) patients with secondary deterioration improved after shunt or valve management and 58% remained without clinical benefit after management. We had a drop-out rate of 15% due to incomplete datasets. Our shunt management reduced the rate of secondary deterioration from 20 to 15%. On the basis of our findings, we developed an algorithm for shunt management. Risk factors for secondary deterioration are the age of the patient at the time of shunting, newly diagnosed neurodegenerative diseases, and overdrainage requiring adjusting the valve to higher-pressure levels. CONCLUSION: Twenty percent of patients with iNPH were at risk for secondary clinical worsening about 3 years after shunt surgery. About one-fourth of these patients benefited for additional years from pressure level management and/or shunt valve revision. Our findings underline the need for long-term follow-ups and intensive shunt management to achieve a favorable long-term outcome for patients with iNPH and VPS.

Sedation of Patients with Acute Aneurysmal Subarachnoid Hemorrhage with Ketamine Is Safe and Might Influence the Occurrence of Cerebral Infarctions Associated with Delayed Cerebral Ischemia.

BACKGROUND: Ketamine has neuroprotective characteristics as well as beneficial cardiocirculatory properties and may thus reduce vasopressor consumption. In contrast, sedation with ketamine (like any other sedative drug) has side effects. This study assesses the influence of ketamine on intracranial pressure (ICP), on the consumption of vasopressors in induced hypertension therapy, and on the occurrence of delayed cerebral ischemia (DCI)-associated cerebral infarctions, with particular focus on the complications of sedation in patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: This is a retrospective, observational study. Sixty-five patients with SAH who underwent a period of sedation were included. The clinical course variables (Richmond Agitation and Sedation scale score, ICP values, consumption of vasopressors, complications of sedation, outcome, and other clinical parameters) were analyzed. Cranial computed tomography results were analyzed. RESULTS: Forty-one patients underwent sedation including ketamine (63.1%). Ketamine decreased the ICP in 92.7% of the cases. Vasopressors was reduced in 53.6%. DCI-associated cerebral infarctions occurred significantly less often in the patient cohort being treated with sedation including ketamine (7.3% vs. 25% in the nonketamine group; P = 0.04). The rate of major complications was not higher in the ketamine group. Outcome was not different regarding the groups if they were sedated with or without ketamine. CONCLUSIONS: Ketamine decreases the ICP and is not associated with a higher rate of complications. The rate of DCI-associated cerebral infarctions was lower in the ketamine group. Ketamine administration led to a reduction of vasopressors used for induced hypertension.

Resident microglia rather than peripheral macrophages promote vascularization in brain tumors and are source of alternative pro-angiogenic factors.

Myeloid cells are an essential part of the glioblastoma microenvironment. However, in brain tumors the function of these immune cells is not sufficiently clarified. In our study, we investigated differential pro-angiogenic activities of resident microglia and peripheral macrophages and their impact on glioma vascularization and progression. Our data demonstrate stable accumulation of microglia/macrophages during tumor growth. These cells often interact with tumor blood vessels correlating with vascular remodeling. Here, we identified resident microglia as well as peripheral macrophages as part of the perivascular niche, primarily contacting endothelial cells. We found overexpression of a variety of pro-angiogenic molecules within freshly isolated microglia/macrophages from glioma. CXCL2, until now a poorly described chemokine, was strongly up-regulated and showed better angiogenic activity than VEGF in vitro. Blocking the CXCL2-CXCR2 signaling pathway resulted in considerably diminished glioma sizes. Additionally, the importance of microglia/macrophages in tumor angiogenesis was confirmed by depletion of these cells in vivo. Vessel density decreased by 50% leading to significantly smaller tumor volumes. Remarkably, selective reduction of resident microglia affected tumoral vessel count comparable to ablation of the whole myeloid cell fraction. These results provide evidence that resident microglia are the crucial modulatory cell population playing a central role in regulation of vascular homeostasis and angiogenesis in brain tumors. Thus, resident microglia represent an alternative source of pro-angiogenic growth factors and cytokines.

MR elastography in a murine stroke model reveals correlation of macroscopic viscoelastic properties of the brain with neuronal density.

The aim of this study was to investigate the influence of neuronal density on viscoelastic parameters of living brain tissue after ischemic infarction in the mouse using MR elastography (MRE). Transient middle cerebral artery occlusion (MCAO) in the left hemisphere was induced in 20 mice. In vivo 7-T MRE at a vibration frequency of 900 Hz was performed on days 3, 7, 14 and 28 (n = 5 per group) after MCAO, followed by the analysis of histological markers, such as neuron counts (NeuN). MCAO led to a significant reduction in the storage modulus in the left hemisphere relative to contralateral values (p = 0.03) without changes over time. A correlation between storage modulus and NeuN in both hemispheres was observed, with correlation coefficients of R = 0.648 (p = 0.002, left) and R = 0.622 (p = 0.003, right). The loss modulus was less sensitive to MCAO, but correlated with NeuN in the left hemisphere (R = 0.764, p = 0.0001). In agreement with the literature, these results suggest that the shear modulus in the brain is reduced after transient ischemic insult. Furthermore, our study provides evidence that the in vivo shear modulus of brain tissue correlates with neuronal density. In diagnostic applications, MRE may thus have diagnostic potential as a tool for image-based quantification of neurodegenerative processes.