Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL).

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (- 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of - 3.0 °C.

Role of aquaporins in hydrocephalus: what do we know and where do we stand? A systematic review.

INTRODUCTION: Glymphatic fluid circulation may be considered the lymphatic system of the brain and the main role of such system seems to be played by aquaporins (AQPs), a family of proteins which regulates water exchange, in particular AQP4 and 1. Alterations of glymphatic fluid circulation through AQPs variations are now emerging as central elements in the pathophysiology of different brain conditions, like hydrocephalus. This systematic review provides an insight about the role of AQPs in hydrocephalus establishment and compensation, investigating their possible role as diagnostic tools or therapeutic targets. METHODS: PubMed database was screened searching for the relevant existing literature in English language published until February 29th 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. RESULTS: A total of 40 articles met the inclusion criteria for our systematic analysis. AQP4 resulted the most studied water channel, followed by AQP1. The changes in cerebrospinal fluid (CSF), brain parenchyma and choroid plexus (CP) in different hydrocephalus type were analyzed. Moreover, important pharmacological interactions regarding AQP and molecules or conditions were discussed. A very interesting result is the general consensus on increase of AQP4 in hydrocephalic patients, unless in patients suffering from idiopathic normal pressure hydrocephalus, where AQP4 shows a tendency in reduction. CONCLUSION: AQP seem to play a central role in the pathophysiology of hydrocephalus and in its compensation mechanisms. Further studies are required to definitively establish their precise roles and their quantitative changes to allow their utilization as diagnostic tools or therapeutic targets.

Retrospective analysis of the clinical and radiological features of 94 consecutive DIPGs patients to investigate the factors determining the development of hydrocephalus and its impact on clinical status and survival.

PURPOSE: There is no consensus in the literature about the impact of hydrocephalus on clinical course and overall survival of diffuse intrinsic pontine gliomas (DIPG) patients as well as about its specific treatment. Authors reviewed a series of DIPG patients to investigate factors related to the onset of hydrocephalus, its treatment, and its impact on clinical course and prognosis. METHODS: A retrospective observational study was performed enrolling pediatric patients affected by DIPG from 2008 to 2018. Clinical and radiological charts were reviewed to find patients' demographic, pathologic and radiologic features in hydrocephalic and non-hydrocephalic patients. In the hydrocephalus cohort, treatment strategy and its effectiveness and complications were analyzed. RESULTS: Ninety-four pediatric patients were enrolled in the study. Patients who developed hydrocephalus showed significantly lesser maximum axial tumor areas than patients without hydrocephalus (respectively 6.5 cm2 vs 16.45 cm2, p < 0.005). Hydrocephalus developed in 33 patients (35%) with an onset interval of 5.24 ± 1.21 months (range 3.2-7.3). The majority of hydrocephalic patients (28 cases, 90%) were treated by ventriculoperitoneal shunt, the remaining 3 patients being treated by endoscopic third ventriculostomy. Mean overall survival was 16.6 months ± 20 months without significative difference between the groups. CONCLUSION: The onset of hydrocephalus occurs in the first moths of the disease story and found a negative correlation with tumor maximal axial diameter. Early treatment of hydrocephalus presents a very low complications rate with satisfying clinical outcome, as it allows the patients to continue the neurooncological therapies being a part of the treatment armamentarium instead of a palliative solution.

Infant ossified cephalohematoma: a review of the surgical management and technical update.

Cephalohematoma is a subperiosteal collection of blood above the skull. It is associated with operative and prolonged deliveries. In most cases the hematoma spontaneously resolves in a short span of time, usually within one month. In a few cases cephalohematoma can become ossified and require surgical treatment. Traditional belief that ossified cephalohematomas are an exclusively cosmetic issue has been called into question by recent description of EEG anomalies associated to a calcified cephalohematoma. We review relevant surgical literature, and we describe a novel variant of Wong's Radial Cap technique by foregoing healthy bone margin removal, removing the cephalohematoma lamellae in a stepwise fashion and using resorbable plaques for fixation. We furthermore review the rationale, timing and step-by-step execution of the procedure. An exemplary case description is discussed.

Cerebral and occipito-atlanto-axial involvement in mucopolysaccharidosis patients: clinical, radiological, and neurosurgical features.

BACKGROUND: Neurosurgical features of mucopolysaccharidosis (MPS) patients mainly involve the presence of cranio-vertebral junction (CVJ) abnormalities and the development of communicating hydrocephalus. CVJ pathology is a critical aspect that severely influences the morbidity and mortality of MPS patients. Hydrocephalus is slowly progressing; it must be differentiated from cerebral atrophy, and rarely requires treatment. The aim of this paper was to review the literature concerning these conditions, highlighting their clinical, radiological, and surgical aspects to provide a practical point of view for clinicians. RESULTS: CVJ involvement may present with cervical pain, unsteady gait, frequent falls, and progressive impairment of autonomous ambulation, an acute tetraplegia even after minor trauma. Magnetic resonance imaging (MRI) of the cervical spine, including active dynamic flexion and extension scans, is the most powerful imaging technique for detecting spinal cord compression at the CVJ in MPS patients. The main radiological features include atlanto-axial subluxation, odontoid hypoplasia, periodontoid soft tissue masses, spinal canal narrowing, and spinal cord compression. Together with MRI, fine-cut computed tomography (CT) scans with coronal and sagittal three-dimensional reconstructions are important diagnostic tools in the preoperative workup thanks to the information gleaned about bone structure conformation and angles. Finally, angio-CT slices are equally useful in preoperative planning, defining vertebral artery position in relation to bony structures. Surgery of the CVJ is proposed both to treat cord compression with MRI signs of myelopathy or as a preventive treatment in patients at high risk of cord damage. Among different surgical options, we always suggest performing decompression and instrumented stabilization. Hydrocephalus may occasionally present clinically with intracranial hypertension symptoms such as headache, vomiting, and high sight impairment. Neurocognitive symptoms may be hidden by the constitutive cognitive impairment. MRI with a study of dynamic cerebrospinal fluid (CSF) flow is helpful to differentiate from ventriculomegaly, which does not require treatment. Ventriculo-peritoneal shunt placement is the gold standard to treat hydrocephalus, although endoscopic third ventriculostomy has recently shown good results in some patients. CONCLUSION: Early recognition of CVJ pathology and hydrocephalus is critical to avoid the development of severe complications. A multidisciplinary approach involving physicians, neuroradiologists, and neurosurgeons is needed to detect such conditions and to select patients eligible for surgery.

Does emergent implantation of a vagal nerve stimulator stop refractory status epilepticus in children?

PURPOSE: Status Epilepticus can be a serious life threatening event in epileptic patients. The definition of refractory or super-refractory Status Epilepticus was based on the therapeutic response to anti-epileptic and anesthetic drugs. Vagal Nerve Stimulation showed efficacy in treating drug-resistant epilepsy but there are only few reports on emergentplacement of Vagal Nerve Stimulator for refractory or super-refractory Status Epilepticus. METHODS: Among 49 children implanted at our Institution with Vagal Nerve Stimulation for drug-resistant epilepsy, the authors retrospectively identified those implanted for refractory or super-refractory Status Epilepticus, according with the current definitions. RESULTS: 4 patients were operated upon at ages ranging 7 to 17 months and reached the programmed output current of 1 mA over a time ranging from 24 to 36 h (fast ramping-up). In 3 out of 4 patient we observed the abrupt of Status Epilepticus; one patient was refractory both to drugs and Vagal Nerve Stimulation and later died, without recovering from SE. At follow up, ranging from 24 to 45 months, the remaining 3 patients showed a decrease of the seizures frequency >80% without relapse of Status Epilepticus; in all the patients, output current and/or Duty Cycle were increased later. CONCLUSION: VNS can be effective in treating refractory or super-refractory Status Epilepticus.

Extensive Dural Ossification After Decompressive Posttraumatic Craniectomy: A Case Report and Review of the Literature.

BACKGROUND: We present a case of almost complete bifrontal dural ossification after decompressive craniectomy for severe traumatic brain injury. CASE DESCRIPTION: A 6-year-old boy was brought to the emergency room after a severe traumatic brain injury (Glasgow Coma Scale/Score 7). Due to rapidly increasing intracranial pressure values (>20 mm Hg) refractory to conservative therapy and in the absence of focal lesions justifying the neurological status, a bicoronal decompressive craniectomy was performed. The patient underwent reconstructive bifrontal cranioplasty with autologous bone 110 days after surgery. Preoperative computed tomography scans showed an abnormal hyperdense layer surrounding both frontal lobes. During the procedure, widespread islets of eggshell-shaped bony tissue were found covering the pericranium and the dura mater. They were laboriously removed from the underlying tissues. Two months later computed tomography scans did not show evidence of calcification at the level of the frontal lobes or signs of bone reabsorption or epidural collections. CONCLUSIONS: We focus on the clinical implications of this phenomenon, in terms of its surgical management and how it may influence the timing of cranioplasty. Furthermore, we discuss the main pathophysiologic models described in the literature.

Safety and efficacy of Endoscopic Third Ventriculostomy in Diffuse Intrinsic Pontine Glioma related hydrocephalus: a Systematic Review.

OBJECT: Diffuse Intrinsic Pontine Gliomas (DIPG) related hydrocephalus occurs as the result of tumor growth and Aqueduct obstruction. There is no consensus about the best surgical option, thus a review has been performed to clarify the rate of success, complications and possible issues of Endoscopic Third Ventriculostomy (ETV) in comparison to the other available techniques. METHODS: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and it was registered with the PROSPERO International Prospective Register of Systematic Reviews(CRD42018089001). MEDLINE, Web of Knowledge and EMBASE were searched for published series in which ETV was performed to treat hydrocephalus in DIPG patients. RESULTS: Six studies were included. Two further cases coming from our experience were added, for a total amount of 55 patients treated through either ETV, VPS or Ventriculocisternal shunt according to Torkildsen. 86% of patients who underwent ETV experienced clinical improvement after surgery (p-value 0.03). Torkildsen shunt placement was associated to 50% failure rate. Two patients implanted with VPS developed symptoms of shunt malfunction and increased ventricular sizes (10%). Fisher's exact test was applied to compare efficacy of VPS and ETV with no statistical difference between the two group (p-value 0,17). Patients who underwent ETV did not experienced major complications and no procedural abortion was observed. CONCLUSIONS: ETV is an effective and safe treatment option, associated to a low complications rate and a high success rate. Evidences from this review suggest to consider ETV as the first line treatment of hydrocephalus in DIPG patients.

Intracerebral hemorrhage in Intensive Care Unit: early prognostication fallacies. A single center retrospective study.

BACKGROUND: Intracerebral hemorrhage (ICH) admitted to Intensive Care is deem of poor prognosis. The aim of this study was to compare observed and predicted 30-day mortality and to evaluate long term functional outcome in a consecutive ICH cohort. METHODS: Retrospective analysis of prospectively collected data of ICH patients managed in a Neuro-ICU from 2012 to 2015. RESULTS: Out of 136 consecutive patients, 34 (25%) had "withholding of life-sustaining treatment" (WLST) order and 102 (75%) received a "full treatment" (FT). WLST cohort: median (IQR): 72 (70-77) years old, Glasgow Coma Scale (GCS) 4 (3-4) at admission, ICH volume 114 cm3 (68-152); all patients died during neuro-ICU recovery, 28 (82%) patients had brain death diagnosis and 15 (54%) of these were organ donors. FT cohort: 67 (51-73) years old, GCS 9 (6-12) at admission, ICH volume 46 (24-90) cm3, neurosurgery for clot removal in 65 (64%) (P<0.05 vs. WLST cohort for each of previously listed variables); 13 (13%) patients died during neuro-ICU recovery, of these 11 (85%) patients had brain death diagnosis and 4 (36%) of them were organ donors. Overall 30-day observed mortality for FT group was 18% (95% CI: 11-26%). Patients with ICH Score 1, 2, 3, 4+ had 0%, 10%, 16% and 26% 30-day mortality, respectively (P<0.01 vs. ICH Score). Full treatment group 180-day mortality was 32% (95% CI: 24-42%). Modified Rankin Scale (mRS) after one year was ≤3 in 35 (35%), i.e. good recovery, and >3 in 64 (65%). Neurosurgery for clot removal was associated with a lower 30 and 180-day mortality (P=0.01 and P=0.03, respectively) and along with GCS at admission it was an independent significant prognostic factor. CONCLUSIONS: Mortality and functional outcome is less severe than predicted in patients with ICH receiving a full medical and/or surgical treatment.

The Disease of the Italian Poet Giacomo Leopardi (1798-1837): A Case of Juvenile Ankylosing Spondylitis in the 19th Century?

Some authors sustained that the pessimistic thought of the Italian writer and philosopher Giacomo Leopardi (1798-1837) may be attributed to his unhappy life, characterized by several health problems. His philosophical theories appear as the result of depressive and melancholic state, related to his precarious health conditions, so limiting their intrinsic values. Several authors formulated various hypotheses on the diseases that Leopardi suffered from and postulated different theories on the cause of his early death. This article assumed that Leopardi may have been affected by juvenile ankylosing spondylitis, conditioning spinal deformities, relapsing-remitting uveitis, urinary tract and bowel tract problems, and acute arthritis. Chest deformity, as a complication of juvenile ankylosing spondylitis, may have caused progressive cardiorespiratory failure, worsened by recurrent bronchial and pulmonary complications, until his death caused by acute right ventricular heart failure. The acknowledgment of a physical cause of Leopardi's disease contributes to reevaluate his "cosmic pessimism" as an original expression of his thought, so leading a general revaluation of the figure of one of the most important European thinkers of the 19th century.

Brain ultrasound rehearsal before surgery: A pilot cadaver study.

It has been shown that brain ultrasonography (US) is an efficient tool for improving three-dimensional (3D) spatial orientation during neurosurgical interventions. However, it necessitates specific training as it is highly operator-dependent. To date, neurosurgeons have relied solely on intraoperative practice to improve their mastery of brain US; this has obvious limitations. Herein, we consider whether a study of brain US on human cadavers could enable a training platform for neurosurgeons and residents to be developed. Standard two-dimensional (2D) brain US was performed on two human cadavers (one fresh-frozen and one Thiel-prepared) through left frontoparietal, left frontal, right temporal, and left parietal craniotomies. US workflow and image quality were assessed in both preparations. It was possible to assess US in both cadaver preparations; however, the specimen prepared with Thiel-fixation performed better, with superior image quality and specimen usability at room temperature. US images were obtainable through all surgical corridors with the main intracranial anatomical landmarks easily identifiable. US of cadaveric brains is feasible and delivers good quality results. This technique could allow neurosurgeons to develop the expertise required for a successful clinical application preoperatively. Clin. Anat. 30:1017-1023, 2017. © 2017 Wiley Periodicals, Inc.

Effectiveness of Intraventricular Endoscopic Lamina Terminalis Fenestration in Comparison with Standard ETV: Systematic Review of Literature.

BACKGROUND: Endoscopic third ventriculostomy is a consolidated technique for the treatment of hydrocephalus. Despite its effectiveness and feasibility, several technical limitations about its use in certain situations have been described. Lamina terminalis-endoscopic third ventriculostomy (LT-ETV) has been proposed as an alternative technique. Authors systematically reviewed the literature in order to define the effectiveness and limits in comparison with standard ETV. METHODS: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. It has also been registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42016041596). MEDLINE, Web of Knowledge, and EMBASE were independently searched. RESULTS: Seven studies were found to be eligible. A case of ours was added to the series, totaling 41 patients (mean patient age ± SD was 21.6 ± 20.7 years). Endoscopic findings leading surgeons to perform LT-ETV were abnormal ventricular anatomy (24, 57%), inadequate/insufficient interpeduncular subarachnoid space (11, 26%), a combination of both (5, 12%), and intraoperatory, unsatisfactory third ventricle floor fenestration (2, 5%). Most common pathologies were neurocysticercosis (12, 28.57%), aqueductal stenosis (8, 19%), tuberculous meningitis (4, 9.52%), and medulloblastoma (3, 7.14%). A flexible endoscope was the most used device (36 procedures, 86%), while not determining a statistical relevant diminution of complications in comparison with a rigid endoscope (P = 1.0). An overall success rate of 69% was registered, increasing to 89% if just the first year of follow-up was considered. CONCLUSIONS: LT-ETV can be considered a successful technical option when standard ETV cannot be performed, although more complex cerebrovascular anatomy is involved. Therefore we suggest that lateral terminalis fenestration is a valid technical option in experienced hands.

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm3 absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Experimental in-vivo model of intravascular shunting for neurosurgical bypass.

BACKGROUND: Excessively long clamping time and suboptimal position of stitches can influence the anastomosis patency and the clinical outcome in cerebral bypass surgery. Coronary intravascular micro-shunts could represent an innovative solution for neurosurgical bypass, but the hemodynamic properties of these devices should be extensively studied before their translational application. We created an experimental in-vivo model and we analyzed the blood flow and pressure modification induced by the micro-shunt. METHODS: After laparotomy, an intravascular micro-shunt was placed into the aorta of 8 adult rats, simulating a neurosurgical setting in which the shunt is temporary placed inside the receiving cerebral vessel. A fiber-optic pressure sensor was placed in the femoral artery and the blood pressure continuously recorded during the procedure. Using an ultrasound vascular probe, blood flow velocity in aorta was measured at baseline and both proximally and distally to the shunt. RESULTS: After shunt positioning, no significant decrease in blood pressure was observed (mean value 68.57 versus 80.00 mmHg; P=0.48). Distal aortic blood flow, expressed as peak systolic velocity, showed a significant decrease after shunt positioning (mean value 51.88 versus 86.88 cm/sec; P=0.04), with a mean residual blood flow of 63%. Blood flow values recorded immediately upstream to the shunt did not differ from baseline. CONCLUSIONS: This is the first in-vivo experimental study concerning the hemodynamic properties of an intravascular micro-shunt. Our results demonstrate that this device provides a considerable blood out-flow without significant changes in blood pressure, suggesting that specific neurosurgical micro-shunts might be developed.

Multi-site laser Doppler flowmetry for assessing collateral flow in experimental ischemic stroke: Validation of outcome prediction with acute MRI.

High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffusion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.