Stroke induces disease-specific myeloid cells in the brain parenchyma and pia.

Inflammation triggers secondary brain damage after stroke. The meninges and other CNS border compartments serve as invasion sites for leukocyte influx into the brain thus promoting tissue damage after stroke. However, the post-ischemic immune response of border compartments compared to brain parenchyma remains poorly characterized. Here, we deeply characterize tissue-resident leukocytes in meninges and brain parenchyma and discover that leukocytes respond differently to stroke depending on their site of residence. We thereby discover a unique phenotype of myeloid cells exclusive to the brain after stroke. These stroke-associated myeloid cells partially resemble neurodegenerative disease-associated microglia. They are mainly of resident microglial origin, partially conserved in humans and exhibit a lipid-phagocytosing phenotype. Blocking markers specific for these cells partially ameliorates stroke outcome thus providing a potential therapeutic target. The injury-response of myeloid cells in the CNS is thus compartmentalized, adjusted to the type of injury and may represent a therapeutic target.

A case report of prostate cancer with leptomeningeal metastasis.

BACKGROUND: Prostate cancer is the most prevalent cancer in men. However, leptomeningeal involvement by prostate carcinoma is a rare event. CASE: Here, we report a 69-year-old patient with castration-resistant metastatic prostate cancer who presented with headache and ataxia. Brain MRI revealed a huge invasive interaxial mass at right occipital lobe with diffuse thickening and enhancement of meninges, the arachnoid, and the pia mater, and he was diagnosed with leptomeningeal carcinomatosis. The patient received whole brain radiotherapy. CONCLUSION: Despite the fact that brain and leptomeningeal metastases are not very common in patients with prostate cancer, signs and symptoms of nervous system disorders should be assessed carefully, and consideration of such unusual metastases must be considered.

Resection of Cervical Intradural Extramedullary Melanoma Metastasis with Pial Invasion: 2-Dimensional Operative Video.

Intradural extramedullary metastatic melanoma is a rare entity with only 13 other cases reported in the literature.1 Of these, only 3 have been described in the cervical spine.2-4 Metastatic melanoma to the brain has historically portended a grim prognosis; however, due to the paucity of reported intradural lesions, the clinical course, including surgical findings, is less well known. This video illustrates a case of a 59-year-old man with new left arm pain and numbness found to have cervical intradural extramedullary metastatic melanoma (Video 1). This video also demonstrates surgical principles and techniques for removal of a rare cervical intradural extramedullary melanoma metastasis using standard cervical laminectomy with intraoperative ultrasound for tumor localization. Considering its rarity, visualizing the intraoperative resection is important for surgeons who may potentially treat such pathology. Patient consented for the procedures and for publication of the video.

Neonatal Subpial Hemorrhage: Clinical Factors, Neuroimaging, and Outcomes in a Quaternary Care Children's Center.

BACKGROUND: Subpial hemorrhages are underrecognized, underreported, and poorly understood. The spectrum of their clinical manifestations and consequences in neonates has not been fully described. Here, we describe the demographic, clinical, and radiographic characteristics of neonates with subpial hemorrhages. METHODS: We reviewed the medical records and neuroimaging studies of neonates with subpial hemorrhage who were admitted to our neonatal intensive care unit between September 2009 and December 2020. RESULTS: Of 114 neonates with intracranial hemorrhage, 31 (27%) had subpial hemorrhage. The majority of neonates in our cohort were male (68%) and born at term (55%). The most common imaging indication was apneas and/or seizures in 58%. Common comorbid conditions included cardiorespiratory failure (42%), hypoxic-ischemic encephalopathy (26%), and coagulopathy (23%). Subpial hemorrhages were multifocal in 45% of neonates, located in the temporal lobe in 45% of neonates, and tended to be larger in neonates with coagulopathy, birth trauma, or hydrocephalus requiring neurosurgical intervention. Subpial hemorrhage was associated with another type of intracranial bleed in 77% of cases and with arterial ischemic stroke in 16% of cases. Of 17 patients with more than one year of follow-up data, 14 (82%) have developmental delay and four (24%) have epilepsy. Of 14 patients with follow-up imaging, 10 (71%) had encephalomalacia subjacent to the subpial hemorrhage. CONCLUSIONS: This is the largest cohort of neonates with subpial hemorrhages to date. Outcome data are limited by duration of follow-up and may be confounded by comorbid conditions and other concurrent hemorrhages. Further study is needed to define the spectrum of risk factors and expected neurological outcomes.

Effect of Durotomy versus Myelotomy on Tissue Sparing and Functional Outcome after Spinal Cord Injury.

Various surgical strategies have been developed to alleviate elevated intraspinal pressure (ISP) following acute traumatic spinal cord injury (tSCI). Surgical decompression of either the dural (durotomy) or the dural and pial (myelotomy) lining of the spinal cord has been proposed. However, a direct comparison of these two strategies is lacking. Here, we compare the histological and functional effects of durotomy alone and durotomy plus myelotomy in a rodent model of acute thoracic tSCI. Our results indicate that tSCI causes local tissue edema and significantly elevates ISP (7.4 ± 0.3 mmHg) compared with physiological ISP (1.7 ± 0.4 mmHg; p < 0.001). Both durotomy alone and durotomy plus myelotomy effectively mitigate elevated local ISP (p < 0.001). Histological examination at 10 weeks after tSCI revealed that durotomy plus myelotomy promoted spinal tissue sparing by 13.7% compared with durotomy alone, and by 25.9% compared with tSCI-only (p < 0.0001). Both types of decompression surgeries elicited a significant beneficial impact on gray matter sparing (p < 0.01). Impressively, durotomy plus myelotomy surgery increased preservation of motor neurons by 174.3% compared with tSCI-only (p < 0.05). Durotomy plus myelotomy surgery also significantly promoted recovery of hindlimb locomotor function in an open-field test (p < 0.001). Interestingly, only durotomy alone resulted in favorable recovery of bladder and Ladder Walk performance. Combined, our data suggest that durotomy plus myelotomy following acute tSCI facilitates tissue sparing and recovery of locomotor function. In the future, biomarkers identifying spinal cord injuries that can benefit from either durotomy alone or durotomy plus myelotomy need to be developed.

Pial arteriovenous fistula with appearance of hemorrhagic tumor: A case report.

INTRODUCTION: Pial arteriovenous fistula (PAVF) is a rare intracranial vascular disease, and its presentation with a huge tumor-resembling thrombus is rarer. PATIENT CONCERNS: A 38-year-old female patient presented with a sudden left-side motor disorder and loss of consciousness. The patient was otherwise in good health and had no history of hypertension or diabetes. During the physical examination, she appeared lethargic and manifested left limb paralysis with level zero muscle strength and a positive pathological reflex. DIAGNOSES: Because imaging failed to rule out a tumor stroke, an intracranial lesion resection was performed immediately. Because the lesion was considered to be a vascular structure, digital subtraction angiography was undertaken before the surgery, and PAVF was diagnosed. INTERVENTIONS: Endovascular embolization was conducted, followed by PAVF and hematoma resection. OUTCOMES: At the 3-month follow up, her left limb muscle strength was level 4, and she could live on her own (Modified Rankin Scale score = 2). CONCLUSIONS: It is noteworthy that PAVF with a large thrombus may appear as a tumor in the initial diagnosis, and therefore it is necessary to perform an intracranial vascular examination in patients with tumor stroke symptoms.

Unexpected and Sudden Death Due to Undiagnosed Moraxella catarrhalis Meningoencephalitis in a 40-day-old Infant: Case Report and Literature Review.

Acute bacterial meningitis in infants and newborns represents a medical emergency and a significant cause of mortality and morbidity worldwide. Moraxella catarrhalis has been considered a microorganism with low pathogenic potential, and only in exceptional cases has it been found to cause meningitis in infants and immunocompetent people. We will now document an unusual case of an unexpected and sudden death of a 40-day-old infant due to acute meningitis from M. catarrhalis, apparently asymptomatic and subsequently diagnosed by an autopsy. According to our knowledge this is the first case of unexpected infant death due to undiagnosed M. catarrhalis meningitis.The suggested case, as well as for the rarity of such a fatal event, should be considered a caution to pediatrics and neonatologists for M. catarrhalis can cause paucisymptomatic meningoencephalitis in infants which can be potentially fatal.From a forensic point of view, an autopsy accompanied by a multidisciplinary assessment is always necessary in cases of unexpected infant deaths to identify the causes.

Surgical Disconnection of a Residual Pediatric Pial Arterio-Venous Fistula Following Partial Embolization: A Case Study.

BACKGROUND: Pial arteriovenous fistulas (AVFs) are rare intracranial vascular lesions consisting of 1 or more feeder arteries connecting directly to a venous system without a nidus, in the subpial space. Because of the high-flow system, they are commonly associated with a large varix. They are thought to represent between 1.6% and 7.3% of all pediatric arteriovenous malformations (AVMs). Morbidity and mortality is high in this condition and surgical or endovascular treatment options are usually considered. There have been limited reports on the clinical features, treatment options, and outcomes of pial AVMs due to its rarity. We present a case study of a pediatric patient in our institution and her clinical course, focusing on her presenting clinical features and management. CASE DESCRIPTION: A 1-year-old girl presents with progressively prominent and dilated facial veins and no other features suggestive of pial AVF. She was diagnosed with pial AVF with two feeder arteries and a large varix on imaging. Embolization was undertaken 3 times before successful surgical disconnection was done. Genetic testing for associated syndromes were all negative. CONCLUSIONS: Prominence of facial veins could be 1 of the more uncommon presenting features of pial AVFs. Genetic testing should always be considered in the pediatric population diagnosed with AVFs because of their association to various syndromes. Despite endovascular embolization being considered the less invasive choice, decision on mode of treatment should be a multifactorial decision.

How to differentiate spinal cord hemangiopericytoma from common spinal cord tumor?

INTRODUCTION: Tumors of the spinal cord are rare and some can be confused with each other. We report a rare spinal cord solitary fibrous tumor/hemangiopericytoma (SFT/HPC), and propose keys to differentiate spinal cord tumors from each other. CASE REPORT: A 67-year-old man presented weakness with recent diffuse sensory disorders in the right lower limb. Spinal MRI revealed a T8-T9 intradural extramedullary mass with spinal cord compression. Gross total resection of a poorly vascularized intradural tumor was achieved. It was an encapsulated extramedullary tumor, which was difficult to separate from the spinal cord due to the presence of pial adhesions. Definitive diagnosis was grade 1 SFT/HPC of the spinal cord. One-year follow-up MRI revealed complete excision without any evidence of residual tumor. CONCLUSION: SFT/HPC is a very rare spinal tumor that can be extramedullary, intramedullary or both. It may perfectly mimic meningioma. The maximal resection is the best treatment, but can be challenging because of the tumor's firm consistency and pial adherences to the spinal cord. Outcome is good in case of gross total resection, but there is a risk of very late recurrence, requiring long-term follow-up.

Ultrastructural and Molecular Characterization of Platelet-derived growth factor Beta-Positive Leptomeningeal Cells in the Adult Rat Brain.

The leptomeninges, referring to the arachnoid and pia mater and their projections into the perivascular compartments in the central nervous system, actively participate in diverse biological processes including fluid homeostasis, immune cell infiltrations, and neurogenesis, yet their detailed cellular and molecular identities remain elusive. This study aimed to characterize platelet-derived growth factor beta (PDGFR-ß)-expressing cells in the leptomeninges in the adult rat brain using light and electron microscopy. PDGFR-ß+ cells were observed in the inner arachnoid, arachnoid trabeculae, pia mater, and leptomeningeal sheath of the subarachnoid vessels, thereby forming a cellular network throughout the leptomeninges. Leptomeningeal PDGFR-ß+ cells were commonly characterized by large euchromatic nuclei, thin branching processes forming web-like network, and the expression of the intermediate filaments nestin and vimentin. These cells were typical of active fibroblasts with a well-developed rough endoplasmic reticulum and close spatial correlation with collagen fibrils. Leptomeningeal PDGFR-ß+ cells ensheathing the vasculature in the subarachnoid space joined with pial PDGFR-ß+ cells upon entering the cortical parenchyma, yet perivascular PDGFR-ß+ cells in these penetrating vessels underwent abrupt changes in their morphological and molecular characteristics: they became more flattened with loss of immunoreactivity for nestin and vimentin and deficient collagen deposition, which was indicative of inactive fibroblasts termed fibrocytes. In the cortical parenchyma, PDGFR-ß immunoreactivity was almost exclusively localized to larger caliber vessels, and significantly decreased in capillary-like microvessels. Collectively, our data identify PDGFR-ß as a novel cellular marker for leptomeningeal fibroblasts comprising the leptomeninges and perivascular adventitial cells of the subarachnoid and penetrating large-sized cortical vasculatures.

Spinal subpial delivery of AAV9 enables widespread gene silencing and blocks motoneuron degeneration in ALS.

Gene silencing with virally delivered shRNA represents a promising approach for treatment of inherited neurodegenerative disorders. In the present study we develop a subpial technique, which we show in adult animals successfully delivers adeno-associated virus (AAV) throughout the cervical, thoracic and lumbar spinal cord, as well as brain motor centers. One-time injection at cervical and lumbar levels just before disease onset in mice expressing a familial amyotrophic lateral sclerosis (ALS)-causing mutant SOD1 produces long-term suppression of motoneuron disease, including near-complete preservation of spinal α-motoneurons and muscle innervation. Treatment after disease onset potently blocks progression of disease and further α-motoneuron degeneration. A single subpial AAV9 injection in adult pigs or non-human primates using a newly designed device produces homogeneous delivery throughout the cervical spinal cord white and gray matter and brain motor centers. Thus, spinal subpial delivery in adult animals is highly effective for AAV-mediated gene delivery throughout the spinal cord and supraspinal motor centers.

Autoregulation assessment by direct visualisation of pial arterial blood flow in the piglet brain.

Impairment of cerebrovascular autoregulation (CAR) is common after brain injury, although the pathophysiology remains elusive. The mechanisms of vascular dysregulation, their impact on brain function, and potential therapeutic implications are still incompletely understood. Clinical assessment of CAR remains challenging. Observational studies suggest that CAR impairment is associated with worse outcomes, and that optimization of cerebral blood flow (CBF) by individual arterial blood pressure (ABP) targets could potentially improve outcome. We present a porcine closed cranial window model that measures the hemodynamic response of pial arterioles, the main site of CBF control, based on changes in their diameter and red blood cell velocity. This quantitative direct CAR assessment is compared to laser Doppler flow (LDF). CAR breakpoints are determined by segmented regression analysis and validated using LDF and brain tissue oxygen pressure. Using a standardized cortical impact, CAR impairment in traumatic brain injury can be studied using our method of combining pial arteriolar diameter and RBC velocity to quantify RBC flux in a large animal model. The model has numerous potential applications to investigate CAR physiology and pathophysiology of CAR impairment after brain injury, the impact of therapeutic interventions, drugs, and other confounders, or to develop personalized ABP management strategies.

A rare concurrence: gelastic seizures in a patient with right temporal nongalenic pial arteriovenous fistula.

INTRODUCTION: Gelastic seizures are the type of seizures that are most commonly seen in childhood and should be excluded definitely in the differential diagnosis of hypothalamic hamartomas. This seizure type may be accompanied by refractory seizures, cognitive decline, and early puberty. However, etiology may also include other causes different than hypothalamic hamartomas. The seizure may also arise from temporal and frontal region, in addition to hypothalamus. Different clinical findings may be observed based on origin and areas of spread. CONCLUSIONS: In this article, we report a case of gelastic seizure that has been observed by a different cause other than hypothalamic hamartoma which was reported for the first time in the literature.

The pathology and aetiology of subcortical clefts in infants.

In infants, traumatic surface contusions of the brain are rare but subcortical clefts or cysts, variously labelled "contusional tears", "contusional clefts", "cortical tears" or "parenchymal lacerations" have been ascribed to trauma, and are even said to be characteristic of shaking and abuse. We describe the pathology of subcortical clefts or haemorrhages in seven infants. In none were the axonal swellings characteristic of traumatic axonal injury seen in relation to the clefts. Subpial bleeding was associated with clefts in all the cases of recent onset. We hypothesize that subcortical clefts are not due to direct mechanical forces of trauma but are part of a secondary cascade caused by impaired venous drainage which may or may not follow trauma. The finding of subcortical and subpial haemorrhages should prompt a search for CVT. We consider the term "contusion" is not accurate and is misleading.

Congenital pial AVF along the falx cerebri with complete agenesis of the corpus callosum and bilateral parasagittal pachygyria-polymicrogyria secondary to chronic ischemia.

OBJECTIVE: Pial arteriovenous fistula (AVF) is an extremely rare entity due to direct arterial connection with the venous plexus without an intervening capillary network. The objective of this article is to describe a unique case of congenital pial AVF along the interhemispheric falx with complete callosal agenesis and malformation of cortical development within the bilateral anterior cerebral artery territories. We also demonstrated the distinctive feature of temporal stability of the extensive intracranial abnormalities without active intervention. Less than 100 cases have been reported thus far, most of which involve the adult rather than pediatric age group. A comprehensive literature review of congenital pial AVF will also be included. CASE DESCRIPTION: A 5-year-old child presented with headache and complex partial seizures. Imaging of the brain revealed the presence of polymicrogyria-pachygyria in the parasagittal frontoparietal lobes with associated underlying white matter hypodensities. Complete agenesis of the corpus callosum was also seen. In addition, enlarged and tortuous vessels were noted along the interhemispheric falx with no appreciable nidus. Bilateral dilated and tortuous ACAs were seen supplying the network of abnormal vessels along the falx. The radiological findings were stable on a follow-up MRI 12 years later. CONCLUSION: Our reported case adds to current limited knowledge of this rare entity in the pediatric age group, which is traditionally treated aggressively and urgently. Our case demonstrated temporal stability of this lesion with no detrimental complications observed. This suggests that the outcome of pial AVFs with conservative treatment may not be as grim as previously thought.

Intra-operative cerebrospinal fluid sampling versus post-operative lumbar puncture for detection of leptomeningeal disease in malignant paediatric brain tumours.

INTRODUCTION: Leptomeningeal disease is a feared sequelae of malignant paediatric brain tumours. Current methods for its detection is the combined use of cranio-spinal MRI, and CSF cytology from a post-operative lumbar puncture. In this study, the authors hypothesize that CSF taken at the start of surgery, either from an external ventricular drain or neuroendoscope will have equal sensitivity for positive tumour cells, in comparison to lumbar puncture. Secondary hypotheses include positive correlation between CSF cytology and MRI findings of LMD. From a clinical perspective, the key aim of the study was for affected paediatric patients to avoid an additional procedure of a lumbar puncture, often performed under anaesthesia after neurosurgical intervention. METHODS: This is single-institution, retrospective study of paediatric patients diagnosed with malignant brain tumours. Its main aim was to compare cytological data from CSF collected at the time of surgery versus data from an interval lumbar puncture. In addition, MRI imaging of the same cohort of patients was examined for leptomeningeal disease and corroborated against CSF tumour cytology findings. RESULTS: Thirty patients are recruited for this study. Data analysis demonstrates a statistically significant association between our intra-operative CSF and LP sampling. Furthermore, our results also show for significant correlation between evidence of leptomeningeal disease on MRI findings versus intra-operative CSF positivity for tumour cells. CONCLUSION: Although this is a retrospective study with a limited population, our data concurs with potential to avoid an additional procedure for the paediatric patient diagnosed with a malignant brain tumour.

Improving Microcirculatory Reperfusion Reduces Parenchymal Oxygen Radical Formation and Provides Neuroprotection.

BACKGROUND AND PURPOSE: Reperfusion is the most significant determinant of good outcome after ischemic stroke. However, complete reperfusion often cannot be achieved, despite satisfactory recanalization. We hypothesized that microvascular protection was essential for achieving effective reperfusion and, hence, neuroprotection. To test this hypothesis, we have developed an in vivo model to differentially monitor parenchymal and vascular reactive oxygen species (ROS) formation. By comparing the ROS-suppressing effect of N-tert-butyl-α-phenylnitrone (PBN) with its blood-brain barrier impermeable analog 2-sulfo-phenyl-N-tert-butylnitrone (S-PBN), we assessed the impact of vascular ROS suppression alone on reperfusion and stroke outcome after recanalization. METHODS: The distal middle cerebral artery was occluded for 1 hour by compressing with a micropipette and then recanalized (n=60 Swiss mice). ROS formation was monitored for 1 hour after recanalization by intravital fluorescence microscopy in pial vasculature and cortical parenchyma with topically applied hydroethidine through a cranial window. PBN (100 mg/kg) or S-PBN (156 mg/kg) was administered shortly before recanalization, and suppression of the vascular and parenchymal hydroethidine fluorescence was examined (n=22). Microcirculatory patency, reperfusion, ischemic tissue size, and neurological outcome were also assessed in a separate group of mice 1 to 72 hours after recanalization (n=30). RESULTS: PBN and S-PBN completely suppressed the reperfusion-induced increase in ROS signal within vasculature. PBN readily suppressed ROS produced in parenchyma by 88%. S-PBN also suppressed the parenchymal ROS by 64% but starting 40 minutes later. Intriguingly, PBN and S-PBN comparably reduced the size of ischemic area by 65% and 48% (P>0.05), respectively. S-PBN restored the microvascular patency and perfusion after recanalization, suggesting that its delayed parenchymal antioxidant effect could be secondary to improved microcirculatory reperfusion. CONCLUSIONS: Promoting microvascular reperfusion by protecting vasculature can secondarily reduce parenchymal ROS formation and provide neuroprotection. The model presented can be used to directly assess pharmacological end points postulated in brain parenchyma and vasculature in vivo.

Pial Arteriovenous Fistula: A Brief Review and Report of 14 Surgically Treated Cases.

OBJECTIVE: The authors report their successful experience of treating 14 cases of pial arteriovenous fistula (PAVF) by direct surgery. METHODS: During the period January 2010 to April 2017, 14 patients with PAVF were treated by surgery. Only those patients were selected who had a single arterial feeding channel. There were 9 male patients and 5 female patients, and their ages ranged from 5 to 53 years (average, 19 years). Ten patients were younger than 20 years of age. Five patients presented clinical and radiologic features that suggested hemorrhage from the PAVF. Ten patients had seizures. Two patients had hemispheric symptoms or neurologic deficits at the time of presentation. In 12 patients, there were no gross neurologic deficits. The diagnosis was made on the basis of digital subtraction angiography in all patients and computed tomographic angiography in 8 patients. Angiography revealed that the PAVFs in 8 patients were supplied by the middle cerebral artery, in 5 patients by the anterior cerebral artery, and in 1 patient by branches of the basilar artery. Surgical procedures involved identification of the site of fistula, obliteration of the feeding artery, and resection of the entire venous varix. RESULTS: The PAVF was successfully excluded from circulation in all patients. There were no neurologic deficits related to the surgical procedure. CONCLUSIONS: Direct surgical resection of the entire PAVF is a safe, effective, and probably curative method of treatment.