Unravelling pituitary tumours in medically treated patients with acromegaly: the impact of systematic MRI reassessment.

BACKGROUND: In acromegaly, the primary tumor is usually found during magnetic resonance imaging (MRI) of the pituitary gland. A remnant tumor after surgery is, however, harder to depict. When a tumor is missed, the remaining option is usually lifelong pharmacological treatment. PURPOSE: To identify tumors by reassessment of all available MRI scans in pharmacologically treated patients, operated or not, and to compare our results with the routine MRI reports. MATERIAL AND METHODS: Adult patients diagnosed with acromegaly and managed at a tertiary care center between 2005 and 2021 and currently on pharmacological treatment were included. MRI scans were evaluated in a standardized manner and classified independently by a radiologist and an endocrinologist into "certain," "suspected," or "no tumor." In case of disagreement, consensus was achieved with a senior neuroradiologist. The results were compared using the clinical radiologists' routine MRI reports. RESULTS: We identified certain and suspected tumors in 29/74 and 36/74 patients, respectively. No tumor was identified in nine patients. In five of these, no MRI contrast agent was given. Discrepancy between our results and the routine MRI reports was found in 31/74 patients (P = 0.01). In 22 patients, the routine reports described no tumor while we identified certain tumors in 2/22 patients and suspected tumors in 13/22 patients. CONCLUSION: In most patients with pharmacologically treated acromegaly, we identified a certain or suspected pituitary tumor. These findings were more frequent compared to the routine MRI reports. Based on our results, patients will be considered for a change in long-term treatment modality.

Cognitive and everyday functioning after bacterial brain abscess: a prospective study of functional recovery from 8 weeks to 1 year post-treatment.

OBJECTIVE: A bacterial brain abscess may damage surrounding brain tissue by mass effect, inflammatory processes, and bacterial toxins. The aim of this study was to examine cognitive and functional outcomes at 8 weeks and 1 year following acute treatment. METHODS: Prospective study of 20 patients with bacterial brain abscess (aged 17-73 years; 45% females) with neuropsychological assessment at 8 weeks and 1 year post-treatment. Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and Patient Competence Rating Scale (PCRS) were used to assess everyday functioning and administered to patients and informants. RESULTS: Cognitive impairment was found in 30% of patients at 8 weeks and 22% at 1 year. Significant improvements were seen on tests of perceptual reasoning, attention, verbal fluency, and motor abilities (p < 0.05). At 1 year, 45% had returned to full-time employment. Nevertheless, patients and their informants obtained scores within the normal range on measures of everyday functioning (PCRS and BRIEF-A) at 8 weeks and 1 year. No significant improvements on these measures emerged over time. CONCLUSION: Residual long-term cognitive impairment and diminished work ability affected 22% and 45% of patients one year after BA. Persistent cognitive impairment emphasizes the importance of prompt acute treatment and cognitive rehabilitation.

Fatigue and depression at 8 weeks and 1 year after bacterial brain abscess and their relationship with cognitive status.

A bacterial brain abscess (BA) is a focal brain infection with largely unknown long-term implications. This prospective study assessed the frequency of fatigue and symptoms of depression at 8 weeks and 1 year after BA and examined the relationship between fatigue, depressive symptoms, and cognitive status. Twenty BA-patients (age 17-73; 45% female) were assessed for fatigue, depression, memory, and executive functions. Fatigue rates were 40-65% at 8 weeks and 25-33% at 1 year on various fatigue questionnaires. Patient Health Questionnaire indicated symptoms of depression in 10% at the 8-week follow-up only. Relevant comorbidities and vocational outcomes were not associated with fatigue or symptoms of depression. Mean fatigue scores improved significantly between the two-time points. Greater fatigue was related to subjective problems with working memory, inhibition, self-monitoring, and emotional control and worse objective verbal memory performance. Symptoms of depression were associated with one out of two fatigue measures. We conclude that fatigue is common in the first year after BA, and higher levels of fatigue are related to more cognitive problems. Symptoms of clinical depression were rare. These findings underscore fatigue as an important consequence of BA and emphasize the necessity for targeted rehabilitation interventions.

TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours.

PURPOSE: Transforming growth factor-beta receptor 3-like (TGFBR3L) is a pituitary enriched membrane protein selectively detected in gonadotroph cells. TGFBR3L is named after transforming growth factor-beta receptor 3 (TGFBR3), an inhibin A co-receptor in mice, due to sequence identity to the C-terminal region. We aimed to characterize TGFBR3L detection in a well-characterized, prospectively collected cohort of non-functioning pituitary neuroendocrine tumours (NF-PitNETs) and correlate it to clinical data. METHODS: 144 patients operated for clinically NF-PitNETs were included. Clinical, radiological and biochemical data were recorded. Immunohistochemical (IHC) staining for FSHß and LHß was scored using the immunoreactive score (IRS), TGFBR3L and TGFBR3 were scored by the percentage of positive stained cells. RESULTS: TGFBR3L staining was selectively present in 52% of gonadotroph tumours. TGFBR3L was associated to IRS of LHß (median 2 [IQR 0-3] in TGFBR3L negative and median 6 [IQR 3-9] in TGFBR3L positive tumours, p < 0.001), but not to the IRS of FSHß (p = 0.32). The presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-FSH median 5.5 IU/L [IQR 2.9-9.6] and median 3.0 [IQR 1.8-5.6] in TGFBR3L negative and positive tumours respectively, p = 0.008) and P-LH (median 2.8 IU/L [IQR 1.9-3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03). TGFBR3 stained positive in 22% (n = 25) of gonadotroph tumours with no correlation to TGFBR3L. CONCLUSION: TGFBR3L was selectively detected in half (52%) of gonadotroph NF-PitNETs. The association to LHß staining and plasma gonadotropins suggests that TGFBR3L may be involved in hormone production in gonadotroph NF-PitNETs.

Long-term control of acromegaly after pituitary surgery in South-Eastern Norway.

PURPOSE: Sustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors. METHODS: Patients operated for GH-secreting pituitary adenomas between 2005-2020 were included from the local pituitary registry (n = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control. RESULTS: A total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38-59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas (p = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96-0.99), p = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57-1.00), p = 0.053). CONCLUSION: In unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.

Endoscopic four-hands technique for pituitary tumours. / Endoskopisk firehåndsteknikk ved hypofysesvulster.

Tumours in the pituitary fossa region can be resected by endoscopic transnasal surgery using a four-hands technique. The technique, which is atraumatic, safe and minimally invasive, should be the first-line treatment for pituitary tumours and certain skull-base tumours.

ß-Amyloid may accumulate in the human brain after focal bacterial infection: An 18 F-flutemetamol positron emission tomography study.

BACKGROUND AND PURPOSE: ß-Amyloid formation has been suggested to form part of the brain's response to bacterial infection. This hypothesis has been based on experimental animal studies and autopsy studies in humans. We asked if ß-amyloid accumulates locally around a bacterial brain abscess in living human patients. Furthermore, because brain abscess patients may suffer from chronic cognitive symptoms after abscess treatment, we also asked if a brain abscess precipitates accumulation of ß-amyloid in the neocortex in a manner that could explain abscess-related cognitive complaints. METHODS: In a prospective study, we investigated 17 brain abscess patients (age 24-72 years) with 18 F-flutemetamol positron emission tomography on one occasion 1 to 10 months after brain abscess treatment to visualize ß-amyloid accumulation. RESULTS: 18 F-flutemetamol uptake was reduced in the edematous brain tissue that surrounded the abscess remains. On this background of reduced 18 F-flutemetamol signal, three out of 17 patients showed a distinctly increased 18 F-flutemetamol uptake in the tissue immediately surrounding the abscess remains, suggesting accumulation of ß-amyloid. These three patients underwent 18 F-flutemetamol positron emission tomography significantly earlier after neurosurgical treatment (p = 0.042), and they had larger abscesses (p = 0.027) than the rest of the patients. All 17 patients suffered from mental fatigue or some subjective cognitive symptom, such as attention difficulties or memory problems, but in none of the patients was there an increase in neocortical 18 F-flutemetamol signal. CONCLUSIONS: ß-Amyloid may accumulate locally around the abscess remains in some patients with a brain abscess.

How I do it: endoscopic endonasal resection of tuberculum sellae meningioma.

BACKGROUND: Tuberculum sellae meningiomas (TSMs) adherent to neurovascular structures are particularly challenging lesions requiring delicate and precise microneurosurgery. There is an ongoing debate about the optimal surgical approach. METHOD: We describe technical nuances and challenges in TSM resection using the endoscopic endonasal approach (EEA) in two cases of fibrous tumors with adherence to neurovascular structures. The cases are illustrated with a video (case 1) and figures (cases 1 and 2). CONCLUSION: A dedicated team approach and precise microsurgical technique facilitate safe resection of complex TSMs through the EEA.

Cut-off values for sufficient cortisol response to low dose Short Synacthen Test after surgery for non-functioning pituitary adenoma.

OBJECTIVE: The aim was to study the prevalence of secondary adrenal insufficiency before and after surgery for non-functioning pituitary adenomas, as well as determine risk factors for developing secondary adrenal insufficiency. A secondary aim was to determine adequate p-cortisol response to a 1-µg Short Synacthen Test after surgery. DESIGN: Longitudinal cohort study. METHODS: One hundred seventeen patients (52/65 females/males, age 59 years) undergoing primary surgery for clinically non-functioning pituitary adenomas were included. P-cortisol was measured in morning blood samples. Three months after surgery, a Short Synacthen Test was performed. RESULTS: All tumours were macroadenomas (mean size 26.9 mm, range 13-61 mm). The surgical indications were visual impairment (93), tumour growth (16), pituitary apoplexy (6) and headache (2). Before surgery, 17% of the patients had secondary adrenal insufficiency (SAI), decreasing to 15% 3 months postoperatively. Risk of SAI was increased in patients operated for pituitary apoplexy (p < 0.001), while age, sex, tumour size and complication rate were not different from the remaining cohort. Three months after surgery, all patients with baseline p-cortisol ≥ 172 nmol/l (6.2 µg/dl) and peak p-cortisol during Short Synacthen Test ≥ 320 nmol/l (11.6 µg/dl) tapered cortisone unproblematically. In patients with intact hypothalamic-pituitary-adrenal axis, p-cortisol peaked < 500 nmol/l (18.1 µg/dl) during Short Synacthen Test in 48% of patient. CONCLUSION: Pituitary surgery is safe and transsphenoidal surgery rarely causes new SAI. Relying solely on morning p-cortisol for diagnosing secondary adrenal insufficiency gives false positives and the Short Synacthen Test remains useful. A peak p-cortisol ≥ 320 during (11.6 µg/dl) Short Synacthen Test indicates a sufficient response, while < 309 nmol/l (11.2 µg/dl) indicates secondary adrenal insufficiency.

Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.

Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients.

PCSK1N as a tumor size marker and an ER stress response protein in corticotroph pituitary adenomas.

PURPOSE: Silent corticotroph adenoma (SCA) exhibits more tumor aggressiveness features than functioning adenomas (FCA). We aimed to investigate PCSK1N expression in CA and examine if ER stress-induced responses affect cell survival in a corticotroph tumor cell model. METHODS: Clinical and imaging characteristics were recorded in 33 patients with FCA (20 women, 11 macroadenomas) and 18 SCA (8 women, all macroadenomas). Gene expression of proopiomelanocortin (POMC), T-box transcription factor 19(TBX19)/TPIT, proprotein convertase subtilisin/kexin type 1(PCSK1)/PC1/3, and its inhibitor PCSK1N, was measured by RT-qPCR in adenoma tissue.Mouse pituitary corticotroph tumor (AtT-20) cells were treated with tanespimycin (17-AAG), a HSP90 chaperone inhibitor, to induce ER stress, followed by gene and protein analyses. RESULTS: POMC, TPIT, and PCSK1 expression were higher, whereas PCSK1N was lower in FCA compared to SCA. PCSK1N correlated with POMC (rs= -0.514, p <0.001), TPIT (rs= -0.386, p = 0.005), PCSK1 (rs= -0.3691, p = 0.008), and tumor largest diameter (rs= 0.645, p <0.001), in all CA. Induction of ER stress by 17-AAG in AtT-20 cells led to a decrease of POMC and an increase of PCSK1N gene expression at 24h. Moreover, a downregulation of cell cycle, apoptosis, and senescence pathways, and alterations in cell adhesion and cytoskeleton were observed at the protein level. CONCLUSIONS: PCSK1N is higher in SCA compared with FCA, and associated with corticotroph cell markers and tumor size. PCSK1N is likely to be part of the adaptive response to ER stress, potentially conferring a survival advantage to the corticotroph tumor cell in conjunction with other proteins.

Bacterial Brain Abscesses Expand Despite Effective Antibiotic Treatment: A Process Powered by Osmosis Due to Neutrophil Cell Death.

BACKGROUND AND OBJECTIVES: A bacterial brain abscess is an emergency and should be drained of pus within 24 hours of diagnosis, as recently recommended. In this cross-sectional study, we investigated whether delaying pus drainage entails brain abscess expansion and what the underlying mechanism might be. METHODS: Repeated brain MRI of 47 patients who did not undergo immediate pus drainage, pus osmolarity measurements, immunocytochemistry, proteomics, and 18F-fluorodeoxyglucose positron emission tomography. RESULTS: Time from first to last MRI before neurosurgery was 1 to 14 days. Abscesses expanded in all but 2 patients: The median average increase was 23% per day (range 0%-176%). Abscesses expanded during antibiotic therapy and even if the pus did not contain viable bacteria. In a separate patient cohort, we found that brain abscess pus tended to be hyperosmolar (median value 360 mOsm; range 266-497; n = 14; normal cerebrospinal fluid osmolarity is ∼290 mOsm). Hyperosmolarity would draw water into the abscess cavity, causing abscess expansion in a ballooning manner through increased pressure in the abscess cavity. A mechanism likely underlying pus hyperosmolarity was the recruitment of neutrophils to the abscess cavity with ensuing neutrophil cell death and decomposition of neutrophil proteins and other macromolecules to osmolytes: Pus analysis showed the presence of neutrophil proteins (protein-arginine deiminases, citrullinated histone, myeloperoxidase, elastase, cathelicidin). Previous studies have shown very high levels of osmolytes (ammonia, amino acids) in brain abscess pus. 18F-fluorodeoxyglucose positron emission tomography showed focal neocortical hypometabolism 1 to 8 years after brain abscess, indicating long-lasting damage to brain tissue. CONCLUSION: Brain abscesses expand despite effective antibiotic treatment. Furthermore, brain abscesses cause lasting damage to surrounding brain tissue. These findings support drainage of brain abscesses within 24 hours of diagnosis.

Minimally invasive microsurgical resection of primary, intradural spinal tumours using a tubular retraction system.

STUDY DESIGN: This is a retrospective review of prospectively collected data. BACKGROUND: Primary, intradural spinal tumours have traditionally been microsurgically resected following macrosurgical laminectomy or laminoplasty. We hypothesize that approach-related morbidity can be reduced with less-invasive approaches; we have therefore implemented a minimally invasive approach, with the assistance of a tubular retraction system, for microsurgical resection of primary intradural spinal tumours. METHODS: From January 2007 to December 2009, 54 patients underwent surgery for a spinal intradural tumour. Of these, nine patients who underwent minimally invasive posterior unilateral transmuscular surgery using a tubular retraction system were included in this study. Resection grade and surgery-related complications were retrospectively reviewed. RESULTS: All tumours were totally resected (verified by postoperative magnetic resonance imaging). There were no post-operative complications. Eight of the nine patients were mobilized on the day of surgery or on post-operative day 1. One patient was mobilized on post-operative day 2. CONCLUSIONS: Selected primary, intradural spinal tumours can be safely and successfully resected using a minimally invasive posterior unilateral transmuscular approach with the assistance of a tubular retraction system.

Pro-inflammatory cytokines in cystic glioblastoma: A quantitative study with a comparison with bacterial brain abscesses. With an MRI investigation of displacement and destruction of the brain tissue surrounding a glioblastoma.

Cystic glioblastomas are aggressive primary brain tumors that may both destroy and displace the surrounding brain tissue as they grow. The mechanisms underlying these tumors' destructive effect could include exposure of brain tissue to tumor-derived cytokines, but quantitative cytokine data are lacking. Here, we provide quantitative data on leukocyte markers and cytokines in the cyst fluid from 21 cystic glioblastomas, which we compare to values in 13 brain abscess pus samples. The concentration of macrophage/microglia markers sCD163 and MCP-1 was higher in glioblastoma cyst fluid than in brain abscess pus; lymphocyte marker sCD25 was similar in cyst fluid and pus, whereas neutrophil marker myeloperoxidase was higher in pus. Median cytokine levels in glioblastoma cyst fluid were high (pg/mL): TNF-α: 32, IL-6: 1064, IL-8: 23585, tissue factor: 28, the chemokine CXCL1: 639. These values were not significantly different from values in pus, pointing to a highly pro-inflammatory glioblastoma environment. In contrast, levels of IFN-γ, IL-1ß, IL-2, IL-4, IL-10, IL-12, and IL-13 were higher in pus than in glioblastoma cyst fluid. Based on the quantitative data, we show for the first time that the concentrations of cytokines in glioblastoma cyst fluid correlate with blood leukocyte levels, suggesting an important interaction between glioblastomas and the circulation. Preoperative MRI of the cystic glioblastomas confirmed both destruction and displacement of brain tissue, but none of the cytokine levels correlated with degree of brain tissue displacement or peri-tumoral edema, as could be assessed by MRI. We conclude that cystic glioblastomas are highly pro-inflammatory environments that interact with the circulation and that they both displace and destroy brain tissue. These observations point to the need for neuroprotective strategies in glioblastoma therapy, which could include an anti-inflammatory approach.

Glioblastoma microenvironment contains multiple hormonal and non-hormonal growth-stimulating factors.

BACKGROUND: The growth of malignant tumors is influenced by their microenvironment. Glioblastoma, an aggressive primary brain tumor, may have cysts containing fluid that represents the tumor microenvironment. The aim of this study was to investigate whether the cyst fluid of cystic glioblastomas contains growth-stimulating factors. Identification of such growth factors may pave the way for the development of targeted anti-glioblastoma therapies. METHODS: We performed hormone analysis of cyst fluid from 25 cystic glioblastomas and proteomics analysis of cyst fluid from another 12 cystic glioblastomas. RESULTS: Glioblastoma cyst fluid contained hormones within wide concentration ranges: Insulin-like growth factor 1 (0-13.7 nmol/L), insulin (1.4-133 pmol/L), erythropoietin (4.7-402 IU/L), growth hormone (0-0.93 µg/L), testosterone (0.2-10.1 nmol/L), estradiol (0-1.0 nmol/L), triiodothyronine (1.0-11.5). Tumor volume correlated with cyst fluid concentrations of growth hormone and testosterone. Survival correlated inversely with cyst fluid concentration of erythropoietin. Several hormones were present at concentrations that have been shown to stimulate glioblastoma growth in vitro. Concentrations of erythropoietin and estradiol (in men) were higher in cyst fluid than in serum, suggesting formation by tumor or brain tissue. Quantitatively, glioblastoma cyst fluid was dominated by serum proteins, illustrating blood-brain barrier leakage. Proteomics identified several proteins that stimulate tumor cell proliferation and invasiveness, others that inhibit apoptosis or mediate adaption to hypoxia and some that induce neovascularization or blood-brain barrier leakage. CONCLUSION: The microenvironment of glioblastomas is rich in growth-stimulating factors that may originate from the circulation, the tumor, or the brain. The wide variation in cyst fluid hormone concentrations may differentially influence tumor growth.

The proteome of pus from human brain abscesses: host-derived neurotoxic proteins and the cell-type diversity of CNS pus.

OBJECTIVE What determines the extent of tissue destruction during brain abscess formation is not known. Pyogenic brain infections cause destruction of brain tissue that greatly exceeds the area occupied by microbes, as seen in experimental studies, pointing to cytotoxic factors other than microbes in pus. This study examined whether brain abscess pus contains cytotoxic proteins that might explain the extent of tissue destruction. METHODS Pus proteins from 20 human brain abscesses and, for comparison, 7 subdural empyemas were analyzed by proteomics mass spectrometry. Tissue destruction was determined from brain abscess volumes as measured by MRI. RESULTS Brain abscess volume correlated with extracellular pus levels of antibacterial proteins from neutrophils and macrophages: myeloperoxidase (r = 0.64), azurocidin (r = 0.61), lactotransferrin (r = 0.57), and cathelicidin (r = 0.52) (p values 0.002-0.018), suggesting an association between leukocytic activity and tissue damage. In contrast, perfringolysin O, a cytotoxic protein from Streptococcus intermedius that was detected in 16 patients, did not correlate with abscess volume (r = 0.12, p = 0.66). The median number of proteins identified in each pus sample was 870 (range 643-1094). Antibiotic or steroid treatment prior to pus evacuation did not reduce the number or levels of pus proteins. Some of the identified proteins have well-known neurotoxic effects, e.g., eosinophil cationic protein and nonsecretory ribonuclease (also known as eosinophil-derived neurotoxin). The cellular response to brain infection was highly complex, as reflected by the presence of proteins that were specific for neutrophils, eosinophils, macrophages, platelets, fibroblasts, or mast cells in addition to plasma and erythrocytic proteins. Other proteins (neurofilaments, myelin basic protein, and glial fibrillary acidic protein) were specific for brain cells and reflected damage to neurons, oligodendrocytes, and astrocytes, respectively. Pus from subdural empyemas had significantly higher levels of plasma proteins and lower levels of leukocytic proteins than pus from intracerebral abscesses, suggesting greater turnover of the extracellular fluid of empyemas and washout of pus constituents. CONCLUSIONS Brain abscess pus contains leukocytic proteins that are neurotoxic and likely participate actively in the excessive tissue destruction inherent in brain abscess formation. These findings underscore the importance of rapid evacuation of brain abscess pus.

Minimally Invasive Microsurgical Resection of Primary, Intradural Spinal Tumors is Feasible and Safe: A Consecutive Series of 83 Patients.

BACKGROUND: To date, the traditional approach to intraspinal tumors has been open laminectomy or laminoplasty followed by microsurgical tumor resection. Recently, however, minimally invasive approaches have been attempted by some. OBJECTIVE: To investigate the feasibility and safety of minimally invasive surgery (MIS) for primary intradural spinal tumors. METHODS: Medical charts of 83 consecutive patients treated with MIS for intradural spinal tumors were reviewed. Patients were followed up during the study year, 2015, by either routine history/physical examination or by telephone consultation, with a focus on tumor status and surgery-related complications. RESULTS: Mean age at surgery was 53.7 yr and 52% were female. There were 49 schwannomas, 18 meningeomas, 10 ependymomas, 2 hemangioblastomas, 1 neurofibroma, 1 paraganglioma, 1 epidermoid cyst, and 1 hemangiopericytoma. The surgical mortality was 0%. In 87% of cases, gross total resection was achieved. The complication rate was 11%, including 2 cerebrospinal fluid leakages, 1 asymptomatic pseudomeningocele, 2 superficial surgical site infections, 1 sinus vein thrombosis, and 4 cases of neurological deterioration. There were no postoperative hematomas, and no cases of deep vein thrombosis or pulmonary embolism. Ninety-three percent of patients were ambulatory and able to work at the time of follow-up. CONCLUSION: This study both demonstrates that it is feasible and safe to remove select, primary intradural spinal tumors using MIS, and augments the previous literature in favor of MIS for these tumors.

Cyst Fluid From Cystic, Malignant Brain Tumors: A Reservoir of Nutrients, Including Growth Factor-Like Nutrients, for Tumor Cells.

BACKGROUND: Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth. OBJECTIVE: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors. METHODS: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors. RESULTS: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3.5) and glutamine at 1.04 mmol/L (0.17-4.2). Lactate was 7.1 mmol/L (2.4-12.5) and correlated inversely with glucose level (r = -0.77; P < .001). Amino acids, including glutamate, varied greatly, but median values were similar to previously published serum values. Ammonia was 75 µmol/L (11-241). B vitamins were present at previously published serum values, and riboflavin, nicotinamide, pyridoxal 5΄-phosphate, and cobalamin were higher in cyst fluid than in cerebrospinal fluid. Inorganic phosphate was 1.25 mmol/L (0.34-3.44), which was >3 times higher than in ventricular cerebrospinal fluid: 0.35 mmol/L (0.22-0.66; P < .001). Tricarboxylic acid cycle intermediates were in the low micromolar range, except for citrate, which was 240 µmol/L (140-590). In cystic metastatic malignant melanomas and lung tumors values were similar to those in GBMs. CONCLUSION: Tumor cysts may be a nutrient reservoir for brain tumors, securing tumor energy metabolism and synthesis of cell constituents. Serum is one likely source of cyst fluid nutrients. Nutrient levels in tumor cyst fluid are highly variable, which could differentially stimulate tumor growth. Cyst fluid glutamate, lactate, and phosphate may act as tumor growth factors; these compounds have previously been shown to stimulate tumor growth at concentrations found in tumor cyst fluid.

Toxic levels of ammonia in human brain abscess.

OBJECTIVE: Brain abscesses could lead to cerebral symptoms through tissue destruction, edema, changes in brain architecture, and increased intracranial pressure. However, the possibility that the pus itself could contribute to symptoms has received little attention. Brain abscesses are areas of tissue destruction, proteolysis, and formation of free amino acids, which are energy substrates for bacteria and possible sources of ammonia. Ammonia is neurotoxic, may cause brain edema, and could contribute to the symptoms of brain abscesses. METHODS: The authors analyzed the extracellular phase of pus from 14 patients with brain abscesses with respect to ammonia and amino acids. For comparison, CSF from 10 patients undergoing external ventricular drainage was included. The ammonia-forming ability of Streptococcus intermedius and Staphylococcus aureus, two common microbial isolates in brain abscesses, was studied in vitro. RESULTS: In brain abscesses ammonia was 15.5 mmol/L (median value; range 1.7-69.2 mmol/L). In CSF ammonia was 29 µmol/L (range 17-55 µmol/L; difference from value in pus: p < 0.001). The total concentration of amino acids in brain abscesses was 1.12-16 times higher than the ammonia concentration (p = 0.011). The median glucose value in pus was 0 mmol/L (range 0-2.1 mmol/L), lactate was 21 mmol/L (range 3.3-26.5 mmol/L), and pH was 6.8 (range 6.2-7.3). In vitro, S. intermedius and S. aureus formed ammonia at 6-7 mmol/L in 24 hours when incubated with 20 proteinogenic amino acids plus g-aminobutyric acid (GABA), taurine, and glutathione at 1 mmol/L. CONCLUSIONS: Intracerebral abscesses contain toxic levels of ammonia. At the concentrations found in pus, ammonia could contribute to the brain edema and the symptoms of brain abscesses.