Microglia and macrophages in glioblastoma: landscapes and treatment directions.

Glioblastoma is the most common primary malignant tumour of the central nervous system and remains uniformly and rapidly fatal. The tumour-associated macrophage (TAM) compartment comprises brain-resident microglia and bone marrow-derived macrophages (BMDMs) recruited from the periphery. Immune-suppressive and tumour-supportive TAM cell states predominate in glioblastoma, and immunotherapies, which have achieved striking success in other solid tumours have consistently failed to improve survival in this 'immune-cold' niche context. Hypoxic and necrotic regions in the tumour core are found to enrich, especially in anti-inflammatory and immune-suppressive TAM cell states. Microglia predominate at the invasive tumour margin and express pro-inflammatory and interferon TAM cell signatures. Depletion of TAMs, or repolarisation towards a pro-inflammatory state, are appealing therapeutic strategies and will depend on effective understanding and classification of TAM cell ontogeny and state based on new single-cell and spatial multi-omic in situ profiling. Here, we explore the application of these datasets to expand and refine TAM characterisation, to inform improved modelling approaches, and ultimately underpin the effective manipulation of function.

Exophytic Brainstem Cavernoma in the Floor of the Fourth Ventricle Midline Suboccipital Approach: 3-Dimensional Operative Video.

This 3-dimensional operative video covers the suboccipital approach to a brainstem cavernoma of the floor of the fourth ventricle. Brainstem cavernomas are low-flow vascular lesions associated with a 2% to 6% annual bleed rate. Repeated bleeds typically result in progressive neurological deficit, and especially for exophytic lesions surgery may arrest this progression without significantly exacerbating pre-existing deficits. The approach to these lesions may be via any standard skull base approach, dictated in each lesion by the presentation to the pial surface. Here, we describe a suboccipital approach to an exophytic cavernoma of the floor of the fourth ventricle, arising caudal to the medial longitudinal fasciculus and facial colliculus. The 38-yr-old male patient had suffered a stepwise neurological deterioration secondary to repeated bleeds, and complete resection of the cavernoma demonstrated here arrested this progression. The patient has provided signed consent to video acquisition and storage at operation, and to publication of this material.

Atypical presentation of delayed communicating hydrocephalus after supratentorial glioma resection with opening of the ventricles.

We report four cases of communicating hydrocephalus, requiring shunt placement, in the subset of patients whose ventricles were breached at the time of glioma resection (a total 97 cases over 3 years). The hydrocephalus in these cases presented without ventricular dilatation on computed tomography (CT) scanning, and in 3 cases without headache. Failure to progress, visual deterioration or cerebrospinal fluid (CSF) leak in the post-operative patient after tumour resection with ventricular opening should alert clinicians to the possibility of hydrocephalus, despite the absence of headache or ventriculomegaly, and lumbar puncture should be performed without delay.