Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer's disease via MFG-E8.

Synapse loss correlates with cognitive decline in Alzheimer's disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in human AD remains to be established. Here we observe astrocytes and microglia from human brains contain greater amounts of synaptic protein in AD compared with non-disease controls, and that proximity to amyloid-ß plaques and the APOE4 risk gene exacerbate this effect. In culture, mouse and human astrocytes and primary mouse and human microglia phagocytose AD patient-derived synapses more than synapses from controls. Inhibiting interactions of MFG-E8 rescues the elevated engulfment of AD synapses by astrocytes and microglia without affecting control synapse uptake. Thus, AD promotes increased synapse ingestion by human glial cells at least in part via an MFG-E8 opsonophagocytic mechanism with potential for targeted therapeutic manipulation.

A rare presentation of a bilateral intracranial parameningeal embryonal rhabdomyosarcoma mimicking vestibular schwannoma in a two-year-old child: a case report.

Intracranial parameningeal rhabdomyosarcomas are rare, aggressive, rapidly progressive paediatric malignancies that carry a poor prognosis. The authors report a case of a 2-year-old boy who initially presented with a left facial palsy, ataxia and, shortly after, bloody otorrhoea. MRI imaging was initially suggestive of a vestibular schwannoma. However, there was rapid progression of symptoms and further MRI imaging showed very rapid increase in tumour size with mass effect and development of a similar tumour on the contralateral side. A histological diagnosis of bilateral parameningeal embryonal rhabdomyosarcoma was made. Despite treatment, progression led to hydrocephalus and diffuse leptomeningeal disease, from which the patient did not survive. Few intracranial parameningeal rhabdomyosarcomas have previously been reported and these report similar presenting symptoms and rapid disease progression. However, this is the first reported case of a bilateral intracranial parameningeal embryonal rhabdomyosarcoma which, on initial presentation and imaging, appeared to mimic a vestibular schwannoma.

Interpretable surface-based detection of focal cortical dysplasias: a Multi-centre Epilepsy Lesion Detection study.

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

Management of traumatic atlanto-occipital dislocation in a 10-year-old with noninvasive halo immobilization: A case report.

Background: Traumatic atlanto-occipital dislocation is an unstable injury of the craniocervical junction. For pediatric patients, surgical arthrodesis of the occipitocervical junction is the recommended management. While having a high success rate for stabilization, the fusion comes with obvious morbidity of limitation in cervical spine flexion, extension, and rotation. An alternative is external immobilization with a conventional halo. Case Description: We describe the case of a 10-year-old boy who was treated successfully for traumatic AOD with a noninvasive pinless halo. Following initial brain trauma management, we immobilized the craniocervical junction with a pinless halo after reducing the atlanto-occipital dislocation. The pinless halo was kept on at all times for the next 3 months. The craniocervical junction alignment was monitored with weekly cervical spine X-rays and CT craniocervical junction on day 15th, day 30th, and day 70th. A follow-up MRI C-spine 3 months from presentation confirmed resolution of the soft-tissue injury and the pinless halo was removed. Dynamic cervical spine X-rays revealed satisfactory alignment in both flexion and extension views. The patient has been followed up for 2 years postinjury and no issues were identified. Conclusion: Noninvasive pinless halo is a potential treatment option for traumatic pediatric atlanto-occipital dislocation. This should be considered bearing in mind multiple factors including age and weight of the patient, severity of the atlanto-occipital dislocation (Grade I vs. Grade II and incomplete vs. complete), concomitant skull and scalp injury, and patient's ability to tolerate the halo. It is vital to emphasize that this necessitates close clinicoradiological monitoring.

Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study.

OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.

Guideline for the management of long tunnelled external ventricular drains in chronic hydrocephalus.

This article reports on the journey of a child with an inoperable hypothalamic-origin pilocytic astrocytoma causing hydrocephalus, which was refractory to treatment with shunts, and required a new approach. With multidisciplinary support, excellent nursing care and parental education, the child's hydrocephalus was managed long term in the community with bilateral long-tunnelled external ventricular drains (LTEVDs). This article describes the patient's journey and highlights the treatment protocols that were created to achieve this feat. Despite the difficulties in initially setting up these protocols, they proved successful and thus the team managing the patient proposed that LTEVDs are a viable treatment option for children with hydrocephalus in the context of inoperable tumours to help maximise quality of life.

Spontaneous subdural haematoma in a neonate requiring urgent surgical evacuation.

We describe the unusual case of a clinically significant subdural haematoma without any underlying cause in a term baby delivered by an elective caesarean section, which required surgical evacuation. We review the literature and describe the presentation, investigation and management options in infants with this infrequent condition.

Management of spontaneous intracranial hypotension: a series of 31 cases over 15-years with a challenging outlier.

Spontaneous intracranial hypotension (SIH) has been classified as a triad of postural headache, low CSF opening pressure (below 60mmH20) and diffuse pachymeningeal gadolinium enhancement on MRI. SIH is due to a non-iatrogenic defect in the dura somewhere along the neuraxis (usually in the spine). The resultant leak depressurizes the system and undermines the buoyancy-providing quality of CSF. In many cases the site of leak is not identified. Epidural blood patch (EBP) is a well-established treatment of SIH but is not always effective. We retrospectively analysed thirty-one cases of SIH who required at least one EBP. They were managed over a fifteen-year period at a single institution. EBP resulted in a significant improvement in headache for 77% of patients. We report in more detail on a particularly challenging outlier where severe SIH resulted in coma. Serial epidural blood patches, burr hole evacuation of chronic subdural haematomata, and infusion of 0.9% NaCl via an intradural spinal catheter were all required to enable long-term recovery.

A novel management proposal for intrinsic brainstem neurenteric cysts: case report.

Neurenteric cysts (NCs) are rare congenital lesions with epithelial mucin-secreting walls. They can occur anywhere along the neural axis, and an intrinsic midbrain cyst is extraordinary. Surgical management may pose a challenge due to the location of the lesion and adhesion of the cyst wall to the surrounding brainstem. The authors describe the first case of pediatric NC that was treated successfully with intracystic interferon-α (IFN-α).A 16-month-old baby girl presented with a 2-week history of progressive croup, vomiting, and swallowing difficulty. MRI revealed a 1.8-cm cystic intrinsic lesion in the pontomedullary region. She initially underwent posterior fossa craniotomy and drainage of the cyst under intraoperative neurophysiology monitoring. Three weeks following the procedure, her symptoms recurred, and follow-up MRI demonstrated cystic recurrence. She underwent repeat aspiration of the cyst and biopsy of the cyst wall, and INF-α-2b was injected into the cystic cavity. Her symptoms improved and completely resolved after 5 months. A 9-month follow-up brain MRI study showed complete resolution of the NC. Intracystic IFN-α injection after cystic content aspiration may be a safe treatment option for the management of intrinsic brainstem NCs. Long-term clinical and radiological follow-up is recommended.

De novo distal middle cerebral artery aneurysm post-excision of intracerebral arteriovenous malformation in an 8-year old.

Cerebral arteriovenous malformations (AVMs) are frequently associated with concurrent aneurysms. These aneurysms are commonly haemodynamically related to the AVM and can be classified into extranidal or intranidal in reference to the AVM nidus. An aneurysm arising from an artery that does not angiographically contribute to the blood flow to the AVM is uncommon. A distal middle cerebral artery (dMCA) aneurysm itself is also a rare presentation, especially in paediatric population. We present a rare case of dMCA aneurysm that was noted after successful surgical management of a ruptured AVM in an 8-year-old child and its management. BACKGROUND: About 10-30% of patients with cerebral arteriovenous malformation (AVM) have an associated artery aneurysm. The majority of these aneurysms are flow-related to the malformation. These aneurysms can be classified into extranidal or intranidal in reference to the AVM nidus Rammos et al Am J Neuroradiol 37:1966-1971, [1]. An aneurysm arising from a different artery that does not angiographically contribute to the blood flow associated with the AVM is less common and would generally be regarded as unrelated to the AVM. Distal cerebral artery aneurysm itself is also a rare presentation, comprising of 1-7% of all middle cerebral artery aneurysm. In children, mycotic infection and dissection are the two most common causes for aneurysm in this location. Unlike in adults, berry aneurysms are uncommon in children. We describe a young patient who was found to have distal middle cerebral artery (dMCA) aneurysm in follow-up DSA (Digital Subtraction Angiogram) after the initial successful surgical treatment for a cerebral frontal AVM. In this particular case, endovascular repair is thought to be the best strategy to treat the aneurysm. However, there still remains a lack of consensus of the best management strategy (surgery or endovascular) in treating flow-related aneurysms in general. This is usually based on an individual case scenario and the treatment is tailored depending on various factors including the expertise of the treating team.

Acute Cerebellitis in Children: A Variable Clinical Entity.

Acute cerebellar ataxia is the most common cause of acute ataxia in children and it usually runs a self-limiting and ultimately benign clinical course. A small proportion of children have evidence of inflammatory swelling in the cerebellum. Many of these children suffer more severe and potentially life-threatening forms of cerebellar ataxia and may need more intensive treatments including urgent neurosurgical treatments. This more severe form of acute cerebellar ataxia is often termed acute cerebellitis. Many children with acute cerebellitis have long-term neurological sequela and evidence of structural cerebellar changes on follow-up imaging. Several patterns of cerebellar inflammation have been described. The authors describe the variabilities in the clinical and radiological patterns of disease in the cases that have been described in the literature.

Comparison of Three Different Cranio-Cervical Decompression Procedures in Children with Chiari Malformation Type I: Does the Surgical Technique Matter?

BACKGROUND/AIMS: A broad spectrum of cranio-cervical decompression techniques (CCD) is employed for the treatment of Chiari malformation type I (CM1). The aim of this study was to compare the clinical and radiological outcome of 3 different CCD performed in a single paediatric centre. METHODS: A retrospective analysis of children treated between 2008 and 2014 was performed. Three different surgical techniques were offered to the patients: an extradural osseo-ligamentous bony decompression (BD), or a BD plus opening of the dura either without duroplasty (DOWD) or with watertight expansile duroplasty (DOPD). The primary clinical outcome was measured by utilizing the Chicago Chiari Outcome Scale (CCOS). RESULTS: Forty-six children underwent 51 CCD: 17 BD, 17 DOWD, and 17 DOPD. The median follow-up period was 46 months (16-98 months). Patients who underwent BD had a shorter length of hospital stay than those who underwent DPTC and DOWD. Clinical improvement, defined by the mean CCOS score, was comparable in patients receiving BD (n = 14.6) and DOPD (n = 14.5), but lower in patients with DOWD (n = 12). Post-operative complications were noted in 7 DOWD patients (41%) and 3 DOPD patients (17.6%). CONCLUSIONS: BD is a safe and effective procedure with comparable clinical and radiological outcomes to DOPD in children with CM1. The risk of post-operative complications and worse clinical outcome was noted to be higher when performing a DOWD.

Long-tunnelled external ventricular drain as a long-term treatment option for hydrocephalus in a child with an unresectable low-grade supratentorial tumor: case report.

The authors report a case of a child with hypothalamic-origin pilocytic astrocytoma and hydrocephalus, which was refractory to treatment with a ventriculoperitoneal shunt due to high CSF protein content. With parental education, the child's hydrocephalus was managed long-term in the community with a long-tunnelled external ventricular drain, which was maintained by his parents. To the authors' knowledge this is the first report of this management option as a long-term measure. No harm has come to the patient. The authors propose long-term, long-tunnelled external ventricular drain as a viable treatment option for such patients.