In this national population-based study of glioma, we present epidemiologic data on incidence, demographics, survival, clinical characteristics and symptoms, and evaluate the association of specific indicators with the grade of glioma. We included 1930 patients registered in the Danish Neuro-Oncology Registry (DNOR) from 2009 to 2014. DNOR is a large-scale national population-based database including all adult glioma patients in Denmark. The age-adjusted annual incidence of histologic verified glioma was 7.3 cases pr. 100,000 person-years. High-grade gliomas were present in 85% and low-grade glioma in 15%. The overall male:female ratio was 3:2 and the mean age at onset was 60 years. Data for WHO grade I, II, III and IV glioma showed several important differences regarding age and sex distribution and symptomatology at presentation. The mean age increased with the grade of glioma and males predominated in all grades. Focal deficits were the most frequent presenting symptom, but among patients with glioma, grade II epileptic seizures were the most frequent symptom. Headache was a rare mono-symptomatic onset symptom. At presentation, higher age, focal deficits and cognitive change for <3 months duration, and headache <1 month were significant independent indicators of high-grade gliomas. Younger age and epileptic seizures for more than 3 months were indicative for low-grade gliomas. Survival rates for glioma grade I-IV showed decreasing survival with increasing grade. Glioma grade I-IV showed high diversity regarding several demographic and clinical characteristics emphasizing the importance of individually tailored disease treatments and support.

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Glioblastoma patients had a poor overall survival but with several specific independent prognostic factors. Extensive cancer treatment was associated with an increasing survival in all age groups, but only half of the patients were sufficiently fit for a full regimen of postoperative combined radiochemotherapy.

Muscle pain can be characterized by local pain and pain referred to distant somatic structures with concomitant cutaneous and deep somatosensory changes. The mechanisms responsible for referred muscle pain are poorly understood. The aim of this study was to study the origin of experimentally-induced referred muscle pain by anaesthetizing the skin overlying the referred pain area and to quantify deep somatosensory changes in the area. Fourteen healthy subjects (mean age = 25.1 years, range 22-34 years) were included in a placebo controlled study consisting of two sessions separated by 1 week. Two stimulation needles were inserted into the right anterior tibial muscle. Electrical stimuli (1Q Hz) were delivered by a computer-controlled constant current stimulator. The intensity required to generate referred pain was determined and the circumference of the referred pain area was marked. At the centre of the area, pressure pain threshold and pinprick perception threshold were determined. Either an anaesthetic cream (EMLA, Astra AB, Sweden) or a placebo cream (Astra AB, Sweden) covered by an occlusive dressing was applied to the marked referred pain area for 90 min. Afterwards, a 600-s stimulation at 150% of the referred pain threshold was induced while the VAS score of referred pain was recorded continuously. Pressure pain threshold and pinprick perception threshold were determined before, during and 5 min after the prolonged stimulation. A significantly lower referred pain visual analogue scale (VAS) score was recorded during the interval from 50 to 150s (p=0.04). The area under the referred pain VAS score vs time curve tended to be lower (22.7%) with the application of skin anaesthetic (p=0.07). The mean referred pain threshold and the mean referred pain area did not differ significantly between the two sessions (p>0.6). No difference was found in pressure pain threshold between the two treatments or between the four recordings during each session (p>0.8). Pinprick perception threshold increased significantly after EML application (p<0.04). Decreased referred pain intensity with application of anaesthetic cream at the referred pain site indicates that referred muscle pain depends on input from the periphery (skin) in humans.

Human glioblastoma multiforme (GBM) is an aggressive cancer with a very poor prognosis. Cripto-1 (CR-1) has a key regulatory role in embryogenesis, while in adult tissue re-expression of CR-1 has been correlated to malignant progression in solid cancers of non-neuronal origin. As CR-1 expression has yet to be described in cerebral cancer and CR-1 is regulated by signaling pathways dysregulated in GBM, we aimed to investigate CR-1 in the context of expression in GBM. The study was performed using enzyme-linked immunosorbent assay (ELISA), Western blotting, polymerase chain reaction (PCR) and immunohistochemistry to analyze the blood and tissue from 28 GBM and 4 low-grade glioma patients. Within the patient cohort, we found high CR-1 protein levels in blood plasma to significantly correlate with a shorter overall survival. We identified CR-1 in different areas of GBM tissue, including perivascular tumor cells, and in endothelial cells. Collectively, our data suggest that CR-1 could be a prognostic biomarker for GBM with the potential of being a therapeutic target.