VEGFR2 signaling drives meningeal vascular regeneration upon head injury.

Upon severe head injury (HI), blood vessels of the meninges and brain parenchyma are inevitably damaged. While limited vascular regeneration of the injured brain has been studied extensively, our understanding of meningeal vascular regeneration following head injury is quite limited. Here, we identify key pathways governing meningeal vascular regeneration following HI. Rapid and complete vascular regeneration in the meninges is predominantly driven by VEGFR2 signaling. Substantial increase of VEGFR2 is observed in both human patients and mouse models of HI, and endothelial cell-specific deletion of Vegfr2 in the latter inhibits meningeal vascular regeneration. We further identify the facilitating, stabilizing and arresting roles of Tie2, PDGFRß and Dll4 signaling, respectively, in meningeal vascular regeneration. Prolonged inhibition of this angiogenic process following HI compromises immunological and stromal integrity of the injured meninges. These findings establish a molecular framework for meningeal vascular regeneration after HI, and may guide development of wound healing therapeutics.

-----Comparison of T1-Post and FLAIR-Post MRI for identification of traumatic meningeal enhancement in traumatic brain injury patients.

Traumatic meningeal enhancement (TME) is a novel biomarker observed on post-contrast fluid-attenuated inversion recovery (FLAIR) in patients who undergo contrast-enhanced magnetic resonance imaging (MRI) after suspected traumatic brain injury (TBI). TME may be seen on acute MRI despite the absence of other trauma-related intracranial findings. In this study we compare conspicuity of TME on FLAIR post-contrast and T1 weighted imaging (T1WI) post-contrast, and investigate if TME is best detected by FLAIR post-contrast or T1WI post-contrast sequences. Subjects selected for analysis enrolled in the parent study (NCT01132937) in 2016 and underwent contrast-enhanced MRI within 48 hours of suspected TBI. Two blinded readers reviewed pairs of pre- and post-contrast T1WI and FLAIR images for presence or absence of TME. Discordant pairs between the two blinded readers were reviewed by a third reader. Cohen's kappa coefficient was used to calculate agreement. Twenty-five subjects (15 males, 10 females; median age 48 (Q1:35-Q3:62; IQR: 27)) were included. The blinded readers had high agreement for presence of TME on FLAIR (Kappa of 0.90), but had no agreement for presence of TME on T1WI (Kappa of -0.24). The FLAIR and T1WI scans were compared among all three readers and 62% of the cases positive on FLAIR could be seen on T1WI. However, 38% of the cases who were read positive on FLAIR for TME were read negative for TME on T1WI. Conspicuity of TME is higher on post-contrast FLAIR MRI than on post-contrast T1WI. TME as seen on post-contrast FLAIR MRI can aid in the identification of patients with TBI.

A case of suicide by double gunshot wounds to the head: the ability to act after the first shot.

A single gunshot (or multiple) does (do) not necessarily lead to immediate loss of consciousness or rapid neurological deficits, so the victim may be able to repeatedly pull the trigger before achieving the lethal effect. Despite multiple gunshot wounds can lead to the suspicious participation of other person to the death of the victim, in the medico-legal literature suicides with multiple gunshot wounds are reported, demonstrating the ability of the victim to act after two or more gunshots. In this case, a 47-years-old man was found dead in a pool of blood in the kitchen of his house. According to findings and analysis, the victim modified a single-shot, pneumatic toy gun branded "Condor" Cal. 7 mm (a gun that is made mainly with "ZAMAK" zinc-based alloy, designed to shoot one soft-polymer bullet at a time, with an initial kinetic energy lower than 1 Joule) into an improvised firearm weapon. With this gun, the victim achieved shooting of two bullets into his head, both entering from the right temporal region of his head, with one stopped in the left occipital lobe and the other one in the left temporal lobe. His death was caused by cranium-meningo-encephalic gunshot wounds. The conditions supporting the hypothesis that the victim was able to fire two shots to his head before the onset of incapacitation (the type of bullets used, the location of injuries and their consequences) and the characteristics that typically allow to distinguish the manner of death (suicide vs homicide) were evaluated. Based on all the collected elements, it was possible to confirm that suicide was the manner of death. This case underlines the importance of evaluating all available elements (post-mortem imaging, autopsy and toxicological findings, ballistics and neuropathological evaluations) to distinguish suicide from homicide and to prevent incorrect conclusions.

Scalp Intravenous Catheter Infiltration Leading to Subdural and Intraparenchymal Fluid Collection and Severe Neurologic Sequelae: A Case Report.

INTRODUCTION: Preterm infants require intravenous (IV) access for administration of medications, IV fluids, and parenteral nutrition. The scalp is a common site for obtaining IV access, and in children with hydrocephalus or wide fontanelles and sutures, there is a high probability of penetrating the meninges and brain matter with the scalp IV needle. If this penetration occurs and remains unnoticed, the contents of the IV infusion can infiltrate into the brain and cause severe brain damage. CASE PRESENTATION: A 3-day-old female neonate, born with myelomeningocele, was receiving total parenteral nutrition through a scalp-vein IV. She experienced a sudden increase in head circumference, a bulging fontanelle, and respiratory distress. Magnetic resonance images demonstrated subdural fluid collection, and the patient underwent emergency surgery. The dura, when opened, exuded milky-white fluid consistent in color with parenteral nutrition. Postoperative imaging showed a parenchymal abnormality caused by the intracranial and intraparenchymal infusion of parenteral nutrition. Four years later, the child had a shunt and had mild cognitive impairment. DISCUSSION: In cases of accidental intracranial administration of parenteral nutrition, we recommend that aggressive therapy be pursued to minimize the risks of developing comorbidities such as meningitis and to allow for maximal functional recovery.

Differential Gene Expression Associated with Meningeal Injury in Acute Mild Traumatic Brain Injury.

Injury to the meninges is not uncommon after traumatic brain injury (TBI), yet minimal research has been directed toward understanding the relevant biology. After a concussive event, the meninges are observed to abnormally enhance on post-contrast magnetic resonance imaging (MRI) in some patients, but not all. The aim of this work is to identify genes differentially expressed in patients with meningeal injury. Patients presenting to the emergency room with suspected TBI received a standard research MRI and blood draw within 48 h of injury. Two groups of patients were included: those with and without abnormal enhancement of the meninges on post-contrast MRI, both without other imaging findings. Groups were compared on microarray gene expression in peripheral blood samples using Affymetrix (Santa Clara, CA) and Partek Genomics Suite (Partek, Inc., St. Louis, MO) software (false discovery rate, <0.05). Forty patients were enrolled with a time from injury to MRI/blood draw of 16.8 h (interquartile range, 7.5-24.1). We observed 76 genes to be differentially expressed in patients with meningeal injury compared to those without, such as receptor for Fc fragment of IgA, multiple C2 domains, transmembrane 2, and G-protein-coupled receptor 27, which have been previously associated with initiating inflammatory mediators, phagocytosis, and other regulatory mechanisms. Post-contrast MRI is able to detect meningeal injury and has a unique biological signature observed through gene expression. These findings suggest that an acute inflammatory response occurs in response to injury to the meninges following a concussion.

Manejo quirúrgico de la aplasia cutis congénita / Surgical management of aplasia cutis congenita

Introducción: La aplasia cutis congénita (ACC) es una malformación congénita rara que afecta sobre todo al cuero cabelludo, aunque puede afectar al pericráneo, el cráneo y la meninges. Las complicaciones pueden llegar a ser fatales, por lo que es necesario un tratamiento oportuno. El tratamiento sigue siendo controvertido, sin encontrar un consenso entre el abordaje conservador y el quirúrgico. El objetivo de este estudio es describir nuestra experiencia en el manejo de la ACC. Material y métodos: Estudio descriptivo retrospectivo de las historias clínicas de los pacientes menores de 14 años con diagnóstico de ACC, atendidos entre el año 2000 y el 2013. Resultados: Veintidós casos de ACC con lesiones que variaban de 1cm (0,79 cm2) a 14cm (153,94 cm2). Dieciocho casos presentaron lesiones en el cuero cabelludo, 3 en extremidades y uno en tronco. Se realizó tratamiento conservador en 9 y quirúrgico en 13 (8 cierres primarios, 2 plastias, 2 injertos cutáneos y un colgajo). Dos pacientes fallecieron por complicaciones de otras patologías no asociadas a la ACC. Conclusiones: La ACC es infrecuente y puede tener un desenlace fatal. Para prevenirla es necesaria una evaluación inicial completa para establecer un tratamiento oportuno. La cirugía es una buena opción terapéutica, sobre todo en defectos con diámetro>4cm (12,6 cm2), ya que disminuye el riesgo de complicaciones mortales (AU)

Introduction: Aplasia cutis congenita (ACC) is a rare congenital malformation that commonly involves the scalp, but can affect pericranium, bone and dura mater. Complications are rare, but can be fatal, so early treatment must be achieved. The treatment remains controversial with no consensus between the conservative and surgical approach. The aim of this study is to describe our experience in the management of ACC. Material and methods: Retrospective review of the medical records of all children up to 14 years diagnosed with ACC and treated between 2000 and 2013. Results: There were a total of 22 cases of ACC with lesions ranging from 1cm (0.79 cm2) to 14cm (153.94 cm2). ACC of the scalp was found in 18 cases, with 3 in extremities and 1 in trunk. Conservative treatment was performed on 9 patients and 13 underwent surgical treatment (8 primary closures, 2 plasties, 2 skin grafts, and 1 skin flap). Two patients died due to complications of other diseases not related with the ACC. Conclusions: ACC is a rare disease that can be fatal. A complete initial assessment to establish early treatment is necessary to prevent this. Surgery should be considered as an initial therapeutic option in defects >4cm (>12.6 cm2) as it prevents the risk of fatal complications (AU)

[Delayed pseudomeningocele as a result of penetrating injury: case report]. / Delici kesici alet yaralanmasina bagli geç gelisen psödomeningosel: Olgu sunumu.

Pseudomeningocele is cerebrospinal fluid collection in an extradural area after meningeal tear. The size of the defect in the dura-arachnoid, the pressure of spinal fluid, and the resistance of the soft tissue presumably determine the size of the pseudocyst. The main symptoms are often: headache, neck pain and myelopathic and radicular signs. Pseudomeningocele is diagnosed by myelography, sonography, computed tomography, and magnetic resonance imaging. We present a case of intraoperative identification nerve root entrapment by pseudomeningocele cyst and postoperative recovery of a patient's neurologic deficit.

A 54-year-old woman with a meningeal lesion compressing the medulla oblongata.

A 54-year-old woman had nausea, vomiting and personality changes since a few weeks. Paresis of the abducens and hypoglossal nerves on the left side, a right sided reduction of the visual field, discrete dysarthri×a and ataxia were diagnosed. Cranial magnetic resonance imaging demonstrated a contrast enhancing circular meningeal lesion of the foramen magnum. Histological examination revealed a granulomatous lesion of the meninges with focal necrosis, vasculitis and neutrophils indicating immune complex reactions. A diagnosis of primary meningeal Wegener's disease was made. Medication with low dose prednisolone led to complete remission of the lesion 1.5 years later.

Imaging of the meninges and the extra-axial spaces.

The separate meningeal layers and extraaxial spaces are complex and can only be differentiated by pathologic processes on imaging. Differentiation of the location of such processes can be achieved using different imaging modalities. In this pictorial review we address the imaging techniques, enhancement and location patterns, and disease spread that will promote accurate localization of the pathology, thus improving accuracy of diagnosis. Typical and unusual magnetic resonance (MR), computed tomography (CT), and ultrasound imaging findings of many conditions affecting these layers and spaces are described.

Inflammatory responses in the rat brain in response to different methods of intra-cerebral administration.

Direct intra-cerebral administration of substances into the brain parenchyma is a common technique used by researchers in neuroscience. However, inflammatory responses to the needle may confound the results obtained following injection of these substances. In this paper we show that the use of a glass micro-needle for intra-cerebral injection reduces mechanical injury, blood-brain barrier breakdown and neutrophil recruitment in response to the injection of vehicle or interleukin-1, compared to using a 26-gauge Hamilton syringe. Therefore, the use of a glass micro-needle to inject substances intra-cerebrally appears to cause minimal injection artefact and should be the method of choice.

Beyond spinal headache: prophylaxis and treatment of low-pressure headache syndromes.

OBJECTIVE: This Evidence-Based Case Management article evaluates and grades the evidence for two anesthesiology-related interventions: prophylaxis after unintentional meningeal puncture and treatment of spontaneous intracranial hypotension (SIH). METHODS: A search was made of relevant English language clinical studies or reports pertinent to the topic of low-pressure headache, but excluding the treatment of meningeal puncture headache. RESULTS: Thirty-seven case reports, case series, and clinical trials were included to develop the best available evidence-based recommendations for the prophylaxis of unintentional meningeal puncture and for the treatment of SIH. CONCLUSION: The highest quality randomized controlled trials suggest that prophylactic epidural blood patch (EBP) does not reduce the incidence of headache after unintentional meningeal puncture. The weight of existing literature supports EBP as an initial treatment of SIH, although its effectiveness does not approach that seen when EBP is used to treat meningeal puncture headache.

The meningeal sheath of the regenerating spinal cord of the eel, Anguilla.

We describe here the meningeal sheath that encloses the spinal cord, and the sheath that develops when the cord regenerates after a total transection. This description is derived from electron and light microscopy. The sheath of the uninjured cord was found to be a single structure of two parts: an outer, thin melanocyte layer and an inner, thicker layer of 2 to 10 rows of fibroblasts, closely associated with collagen and elastic fibers. Soon after cord transection, the injured axons re-grow and, together with the reforming central canal, create a bridge that links the transected cord within 8 days of injury. This bridge is covered at first by a rudimentary meningeal sheath, formed of fibroblasts and macrophages, that later progressively thickens and becomes more compact. By about day 20, the fibroblasts are arranged as 16 to 20 loose rows that include bundles of collagen, oriented along the rostro-caudal axis of the cord. Even after 144 days, the meninx, although substantially thicker than normal because of the numerous fibroblast rows (20 to 30), still lacks the melanocyte layer. In cases in which the meninx at the transection site was mechanically and pharmacologically (6-hydroxydopamine) disrupted, bridge formation was essentially unchanged, and axonal regrowth continued; some regrowing axons, however, extruded from the denuded cord. Accordingly, our findings indicate that although the meningeal sheath is not essential for cord regeneration to take place, it may well facilitate recovery by providing mechanical guidance and support to the regrowing axons.

Congenital predisposition to spontaneous intracranial hypotension: a case report.

Dural rupture, cerebrospinal fluid leakage, and spontaneous intracranial hypotension may complicate significant or minimal spinal trauma and cause chronic headache with a positional component. While such cases typically reflect no pre-existing predilection, we encountered a patient whose cervicothoracic anatomy appeared to predispose him to this complication.

Post-traumatic intradiploic leptomeningeal fistula and cyst.

A 59 year old female patient presented with ataxia and difficulty in walking. The neurological examination revealed right homonymous hemianopia and ataxia. Radiographic evaluation revealed a large occipital intradiploic cyst mainly in the left suboccipital area. There was also moderate hydrocephalus and encephalomalacia of the left occipital pole. Bone window studies also demonstrated a growing fracture extending from the upper pole of the cyst to the vertex. Both pathologies were attributed to child abuse the patient suffered when she was a child. At first surgery, decompression of the cerebellum was followed by duroplasty and acrylic cranioplasty to the posterior cranial fossa. A month later, a shunt had to be inserted for hydrocephalus. At 7 months postoperatively, the patient is well and free of any symptoms or recurrence.

Spontaneous intracranial hypotension.

Spontaneous intracranial hypotension (SIH) is typically manifested by orthostatic headaches that may be associated with one or more of several other symptoms, including pain or stiffness of the neck, nausea, emesis, horizontal diplopia, dizziness, change in hearing, visual blurring or visual field cuts, photophobia, interscapular pain, and occasionally face numbness or weakness or radicular upper-limb symptoms. Cerebrospinal fluid (CSF) pressures, by definition, are quite low. SIH almost invariably results from a spontaneous CSF leak. Only very infrequently is this leak at the skull base (cribriform plate). In the overwhelming majority of patients, the leak is at the level of the spine, particularly the thoracic spine and cervicothoracic junction. Sometimes, documented leaks and typical clinical and imaging findings of SIH are associated with CSF pressures that are consistently within limits of normal. Magnetic resonance imaging of the head typically shows diffuse pachymeningeal gadolinium enhancement, often with imaging evidence of sinking of the brain, and less frequently with subdural fluid collections, engorged cerebral venous sinuses, enlarged pituitary gland, or decreased size of the ventricles. Radioisotope cisternography typically shows absence of activity over the cerebral convexities, even at 24 or 48 hours, and early appearance of activity in the kidneys and urinary bladder, and may sometimes reveal the level of the leak. Although various treatment modalities have been implemented, epidural blood patch is probably the treatment of choice in patients who have failed an initial trial of conservative management. When adequate trials of epidural blood patches fail, surgery can offer encouraging results in selected cases in which the site of the leak has been identified. Some of the spontaneous CSF leaks are related to weakness of the meningeal sac, likely in connection with a connective tissue abnormality.

[Tethered cord syndrome in adults]. / Zespól zakotwiczonego rdzenia kregowego u doroslych.

The authors present a description of three patients in whom symptoms of spinal cord injury developed late after opening of the dural sac of the spinal canal. The material comes from two female and one male patients of age 37-47 years. In the first case the symptoms included increased paraesthesia, pain, paraparesis and sphincter disorders, which appeared 16 years after stab wound of meninges and the spinal cord at Th10. In the second patient, operated on for myelomeningocele at L3-4 at the age of five, sphincter disorders, trophic changes of feet and paraparesis appeared. The third patient was operated on for intra- and extramedullary lipoma at Th9-12. Seven months after the operation symptoms of sphincter disorders, pain, paraesthesia and paraparesis developed. The MR examination showed in all patients an adhesion of the posterior or posterolateral surface of the spinal cord with the dura mater at the sites of injury, which was confirmed intraoperatively. An operative treatment improved the clinical state. The tethering of the cord by the scar was the cause of a non-physiological stretching of the spinal cord on flexion of the body and head. It led to spinal circulation disorders and symptoms of myelopathy. It has been observed that the onset of the symptoms is often caused by sudden stretching of the spinal cord during fall or intense physical exercises. In such cases operative release of the spinal cord from the adhesion is a method of choice.

The pathogenesis and clinical significance of traumatic subdural hygroma.

Subdural hygroma (SDG) is a common post-traumatic lesion. Despite its common occurrence, the pathogenesis and clinical significance are uncertain. The author reviewed the literature to clarify the present knowledge on the pathogenic, diagnostic and therapeutic aspects of this controversial lesion. A trivial trauma can cause a separation of the dura-arachnoid interface, which is the basic requirement for the development of a SDG. If the brain shrinks due to brain atrophy, excessive dehydration or decreased intracranial pressure, fluid collection may develop by a passive effusion. Most SDGs resolve when the brain is well expanded. However, a few SDGs become chronic subdural haematomas, when the necessary conditions persist over several weeks. Since the majority of patients with a SDG do not show a mass effect, surgery is rarely required. Outcome is closely related to the primary head injury not to the SDG itself. The complexity of SDG depends on various factors including the dynamics of absorption and expansion, duration of observation, and indication and rate of surgery, besides variety of the primary head injury in types and severity. SDG is a common epiphenomenon of head injury.

Cranial plate and screw fixation in infancy: an assessment of risk.

Sixty-seven surgeons, members of the International Craniofacial Surgery Society, responded to a questionnaire focused on assessing the incidence and risk of cranial plate and screw translocation intracranially in infants undergoing cranial surgery. Despite screws, plates, and wires being evident intracranially in individual cases, no apparent increase in seizure frequency or susceptibility to head trauma was noted in this preliminary study.