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.

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.

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.

Cerebral collateral flow defines topography and evolution of molecular penumbra in experimental ischemic stroke.

Intracranial collaterals are dynamically recruited after arterial occlusion and are emerging as a strong determinant of tissue outcome in both human and experimental ischemic stroke. The relationship between collateral flow and ischemic penumbra remains largely unexplored in pre-clinical studies. The aim of the present study was to investigate the pattern of collateral flow with regard to penumbral tissue after transient middle cerebral artery (MCA) occlusion in rats. MCA was transiently occluded (90min) by intraluminal filament in adult male Wistar rats (n=25). Intracranial collateral flow was studied in terms of perfusion deficit and biosignal fluctuation analyses using multi-site laser Doppler monitoring. Molecular penumbra was defined by topographical mapping and quantitative signal analysis of Heat Shock Protein 70kDa (HSP70) immunohistochemistry. Functional deficit and infarct volume were assessed 24h after ischemia induction. The results show that functional performance of intracranial collaterals during MCA occlusion inversely correlated with HSP70 immunoreactive areas in both the cortex and the striatum, as well as with infarct size and functional deficit. Intracranial collateral flow was associated with reduced areas of both molecular penumbra and ischemic core and increased areas of intact tissue in rats subjected to MCA occlusion followed by reperfusion. Our findings prompt the development of collateral therapeutics to provide tissue-saving strategies in the hyper-acute phase of ischemic stroke prior to recanalization therapy.

Craniovertebral junction pathological features and their management in the mucopolysaccharidoses.

The mucopolysaccharidoses (MPS) are multisystemic inherited metabolic diseases caused by the deficiency of the enzymes involved in the degradation of glycosaminoglycans (GAGs), which variably involve the central nervous system, heart, lungs, and bones.Undegraded or only partly degraded GAGs accumulate in the extracellular matrix, joint fluid, and connective tissue leading to widespread tissue and organ dysfunction.The introduction of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) has positively affected the natural history of MPS patients and their life expectancy. However, the presence of spinal abnormalities and deposition of GAGs in soft tissues remains nearly unaltered.Abnormalities of the craniovertebral junction (CVJ) and GAG deposits can result in spinal cord compression with slowly progressive myelopathy or acute posttraumatic tetraplegia.The current paper discusses neuroimaging findings in a consecutive series of 42 MPS patients followed at our Center for Metabolic Diseases and their neurosurgical issues.Current recommendations for decompression and fusion will be discussed according to our experience and review of the literature.

Ganglioglioma of the spinal cord in neurofibromatosis type 1.

The oncologic involvement of the spinal cord in neurofibromatosis type 1 (NF1) is not a typical feature of the disease. Here, we present a case of ganglioglioma of the spinal cord in a child with NF1 and try to define if this tumor can be considered coincidental or not. A 4-year-old boy affected by NF1 was diagnosed with a spinal cord-enhancing tumor extending from C4 to D3, with a disappearance in the T2 MRI sequences of the cerebrospinal fluid signal. The patient underwent a subtotal resection. The pathological exam revealed a ganglioglioma. To the best of our knowledge, only 1 other case of spinal cord ganglioglioma has been described in an NF1 patient. We suggest considering ganglioglioma in the differential diagnosis of an NF1 patient with a spinal cord tumor due to its favorable survival rate, especially in relation to the anatomical and surgical issues of this tumor that do not always entail a gross total resection.

The association of neural axis and craniovertebral junction anomalies with scoliosis in Rubinstein-Taybi syndrome.

OBJECT: Rubinstein-Taybi syndrome (RSTS) is a rare condition with characteristic genetic and clinical features. The presence of variable vertebral and neural axis abnormalities has been reported in the literature. We describe the possible association of multiple different spinal anomalies in these patients. RESULTS: The radiological exams of two RSTS patients (a female and male of 11 and 13 years) have been reviewed. Both patients presented the simultaneous association of craniovertebral junction bony abnormalities (occipito-C1 condyle subluxation and posterior C2-C3 arches fusion), Chiari I malformation, spinal cord syrinx, low-lying conus medullaris, and scoliosis. CONCLUSION: An association of different spinal cord anomalies is possible in RSTS patients and has to be investigated with a comprehensive neuroimaging study in order to address the proper treatment and prevent the development of neurologic deficits.

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.

Anatomical correlates for category-specific naming of living and non-living things.

INTRODUCTION: Selective naming categories impairments for living and non-living things are widely reported in brain damaged patients. Electrostimulation mapping was used to study the possible anatomical segregation of living/non-living categories in a prospective series of patients operated on for tumor removal. MATERIALS AND METHODS: Fifty brain mappings (patients with no language impairment; range: 14-80 years; mean: 48 years; 26 males; 5 left handed) were performed in 46 left and 4 right hemispheres using two linguistically controlled tasks (naming for living and non-living things) during an awake surgery procedure. Fifteen regions and four macro cortical areas were designed to analyze the distribution of the interference sites. RESULTS: Over 761 sites stimulated in the lateral hemispheres, 130 naming interferences sites were detected in small cortical areas (<1cm(2)). High individual variability was observed for living/non-living word retrieval localization and organization with a majority (62%) of shared living/non-living interferences. Specific living (12%) or non-living (26%) interferences were found too. In group analysis, no statistical significant anatomical localization was observed for living items in left lateral hemispheric cortex. A statistical significant representation of interference sites for non-living objects was found (Generalized Estimating Equation methodology, z-test=2.28, p=0.027) in the left posterolateral temporoparietal cortex. No influence of histopathology, gender and age on anatomical localization of naming categories was detected. CONCLUSION: The existence of dedicated neural structures for naming non-living things in the left posterolateral temporoparietal cortex is supported by this study although high individual differences exist in the organization of word categories retrieval.

Cavum veli interpositi: just an anatomical variant or a potentially symptomatic CSF compartmentalization?

BACKGROUND: The cavum veli interpositi (CVI) usually is a small CSF-containing abnormality of septum pellucidum, asymptomatic and rare after the age of 3 years. When symptomatic, it is large and can be related to psychiatric disorders, syndromic association of mental retardation and seizures or to hydrocephalus. METHODS: This is the first reported case of an otherwise healthy pediatric patient with a large CVI experiencing episodes of hypertonic loss of consciousness unrelated to epileptic, cardiologic or psychiatric causes without signs of chronic increase in intracranial pressure (ICP). RESULTS: Supposing a CSF compartmentalization in the CVI as the cause of acute poussés of ICP due to block of CSF pathways and considering the severity of the symptoms, an endoscopic fenestration was performed with a reduction of cyst dimensions. CONCLUSION: We suggest considering the fenestration of large CVI even in otherwise asymptomatic patients to avoid the risk of CSF compartmentalization with ICP poussés.

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.

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.

Oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor of the thoracic spine.

Phosphaturic mesenchymal tumors that cause the paraneoplastic syndrome known as oncogenic osteomalacia are rare. The authors report on the case of a 57-year-old man with a history of osteomalacia and in whom was diagnosed a thoracic spine tumor at the T-4 level. Complete tumor resection was accomplished. The histological diagnosis was phosphaturic mesenchymal tumor (mixed connective tissue variant). After lesion removal, the paraneoplastic syndrome resolved. At the 24-month follow-up, no recurrence of the disease was observed. The clinical presentation, surgical technique, and follow-up in this case were reviewed in detail.

Severely symptomatic craniovertebral junction abnormalities in children: long-term reliability of aggressive management.

OBJECTIVES: The treatment of symptomatic cranio-vertebral junction (CVJ) instability in children affected by CVJ abnormalities is a challenge. A series of severely symptomatic children has been reviewed to understand the controversial long-term effectiveness of the aggressive management of CVJ abnormalities, in terms of clinical improvement, spinal stability and growth. METHODS: Three Down syndrome patients, 1 with mucopolysaccharidosis and 1 with os odontoideum (range 3-6 years old) with a CVJ instability determining spinal cord compression with severe neurological deficits (the patients presented at admission a Ranawat III A/III B neurological condition), were consecutively treated at our institution. Medical records, imaging studies, adopted surgical techniques and long-term results were reviewed. Details of the presenting symptoms, clinical and radiological signs were compared to the signs and symptoms at follow-up. RESULTS: The perioperative use of an halo-orthosis, the operative techniques and the timing of rehabilitation were always tailored to the patient's anatomical features. All the patients showed remarkable neurological improvements, along with construct stability and bone fusion without abnormalities of the developing spine. CONCLUSIONS: Considering the effective long-term results, we recommend, even in severely symptomatic children with CVJ abnormalities, a multidisciplinary aggressive tailored treatment of instability with rigid internal fixation.

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.

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.

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.