For many children with craniopharyngiomas, the cost of resection is hypothalamic dysfunction and a poor QOL. By using a preoperative classification system to grade hypothalamic involvement and stratify treatment, the authors were able to minimize devastating morbidity. This was achieved by identifying subgroups in which complete resection or STR, performed by an experienced craniopharyngioma surgeon and with postoperative radiotherapy when necessary, yielded better overall results than the traditional GTR.

The long-term clinical outcome following traumatic brain injury (TBI) can be difficult to predict. Proton magnetic resonance spectroscopy (MRS) has previously been used to demonstrate abnormalities in regions of white matter that appear normal on conventional imaging in patients following TBI. We report MRI and MRS studies of 26 patients performed at an early time point following injury (mean 12 days, n = 21) and at a later time point (mean 6.2 months, n = 15). The proton MRS was acquired from the posterior part of a normal-appearing frontal lobe containing predominantly white matter using stimulated echo acquisition mode to localize, with a relaxation time of 3000 ms and echo time of 30 ms. At both the early and late time points the N:-acetylaspartate/creatine ratio (NAA/Cr) was significantly reduced (P = 0.03, P = 0.005, respectively), the choline/creatine ratio (Cho/Cr) significantly increased (P = 0.001, P = 0.004, respectively) and the myo-inositol/creatine ratio (Ins/Cr) significantly increased (P = 0.03, P = 0.03, respectively) compared with controls. There was a small, but significant, further reduction (P = 0.02) in the NAA/Cr between the two studies in the 10 patients for whom data was available, at both time points. The NAA/Cr acquired at the early time point significantly correlated with the clinical outcome of the patients, assessed using either the Glasgow outcome scale (P = 0.005, n = 17) or the disability rating scale (P < 0.001, n = 17). We conclude that there is a sustained alteration in NAA and Cho. These findings provide possible evidence for cellular injury (NAA loss reflecting neuroaxonal cell damage and raised Cho and Ins reflecting glial proliferation) not visible by conventional imaging techniques. This may be relevant to understanding the extent of disability following TBI.

The findings of this study imply that stereotactic biopsy sampling of a diffuse pontine tumor is a safe procedure, is associated with minimal morbidity, and has a high diagnostic yield. A nonmalignant tumor was identified in two of the 24 patients in whom the imaging findings were characteristic of a malignant infiltrative astrocytoma. With the advent of new treatment protocols, stereotactic biopsy sampling, which would allow specific tumor characterization of diffuse pontine lesions, may become standard.

The majority of tumors arising in the thalamus are astrocytic, of which less than half are high-grade lesions. Histological evaluations should be performed in all patients in whom resection is being considered for discrete lesions. Long-term survival is possible in patients with these tumors.

Microglia, the tissue resident macrophages of the CNS, play critical roles in immune defence, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using an hIPSC-based macrophage model to fine-map a candidate causal variant for Alzheimer’s disease at the BIN1 locus. Our study provides the first population-scale transcriptional map of a critically important cell for human CNS development and disease.

Neuropsychological studies in patients who have suffered traumatic brain injury show that the eventual clinical outcome is frequently worse than might be predicted from using conventional (CT or T(1)/T(2)-weighted MRI) imaging. Furthermore, patients who have sustained an initial mild or moderate injury may show long-term disability. This implies that there may be abnormalities in areas of the brain that actually appear normal on conventional imaging. Proton magnetic resonance spectroscopy studies have shown that N-acetylaspartate and choline-containing compounds can provide measures of cellular injury. We report MRI and proton magnetic resonance spectroscopy studies of 19 head-injured patients performed once the patients were clinically stable (mean 11 days after injury, range 3-38 days). Proton magnetic resonance spectra were acquired from frontal white matter that on conventional MRI appeared normal. The brain N-acetylaspartate/creatine ratio was reduced [patients (mean +/- standard deviation), 1.28 +/- 0.25; controls, 1.47 +/- 0. 24; P = 0.04] and the choline/creatine ratio was increased (patients, 0.85 +/- 0.18; controls, 0.63 +/- 0.10; P < 0.001) compared with controls. When the severity of the injury was assessed using either the Glasgow coma scale or the length of post-traumatic amnesia, the increase in the choline/creatine ratio was significant even in the mildly injured group (P = 0.008 and P = 0.04, respectively). Furthermore, there was a significant correlation (P = 0.008) between the severity of head injury and the N-acetylaspartate/choline ratio. We conclude that there is an early reduction in N-acetylaspartate and an increase in choline compounds in normal-appearing white matter which correlate with head injury severity, and that this may provide a pathological basis for the long-term neurological disability that is seen in these patients.

Experimental studies have reported early reductions in pH, phosphocreatine, and free intracellular magnesium following traumatic brain injury using phosphorus magnetic resonance spectroscopy. Paradoxically, in clinical studies there is some evidence for an increase in the pH in the subacute stage following traumatic brain injury. We therefore performed phosphorus magnetic resonance spectroscopy on seven patients in the subacute stage (mean 9 days postinjury) following traumatic brain injury to assess cellular metabolism. In areas of normal-appearing white matter, the pH was significantly alkaline (patients 7.09 +/- 0.04 [mean +/- SD], controls 7.01 +/- 0.04, p = 0.008), the phosphocreatine to inorganic phosphate ratio (PCr/Pi) was significantly increased (patients 4.03 +/- 1.18, controls 2.64 +/- 0.71, p = 0.03), the inorganic phosphate to adenosine triphosphate ratio (Pi/ATP) was significantly reduced (patients 0.37 +/- 0.10, controls 0.56 +/- 0.19, p = 0.04), and the PCr/ATP ratio was nonsignificantly increased (patients 1.53 +/- 0.29, controls 1.34 +/- 0.19, p = 0.14) in patients compared to controls. Furthermore, the calculated free intracellular magnesium was significantly increased in the patients compared to the controls (patients 0.33 +/- 0.09 mM, controls 0.22 +/- 0.09 mM, p = 0.03)). Proton spectra, acquired from similar regions showed a significant reduction in N-acetylaspartate (patients 9.64 +/- 2.49 units, controls 12.84 +/- 2.35 units, p = 0.03) and a significant increase in choline compounds (patients 7.96 +/- 1.02, controls 6.67 +/- 1.01 units, p = 0.03). No lactate was visible in any patient or control spectrum. The alterations in metabolism observed in these patients could not be explained by ongoing ischemia but might be secondary to a loss of normal cellular homeostasis or a relative alteration in the cellular population, in particular an increase in the glial cell density, in these regions.

Medically intractable epilepsy in children can be treated effectively by surgery. The degree of resection or disconnection of diseased tissue, but not patient age at the time of surgery, is an important factor in achieving epilepsy control. Early surgery is more likely to improve developmental outcome.