Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination

Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways

Role of Tobacco Use in the Etiology of Acoustic Neuroma

Two previous studies suggest that cigarette smoking reduces acoustic neuroma risk; however, an association between use of snuff tobacco and acoustic neuroma has not been investigated previously. The authors conducted a case-control study in Sweden from 2002 to 2007, in which 451 cases and 710 population-based controls completed questionnaires. Cases and controls were matched on gender, region, and age within 5 years. The authors estimated odds ratios using conditional logistic regression analyses, adjusted for education and tobacco use (snuff use in the smoking analysis and smoking in the snuff analysis). The risk of acoustic neuroma was greatly reduced in male current smokers (odds ratio (OR) = 0.41, 95% confidence interval (CI): 0.23, 0.74) and moderately reduced in female current smokers (OR = 0.70, 95% CI: 0.40, 1.23). In contrast, current snuff use among males was not associated with risk of acoustic neuroma (OR = 0.94, 95% CI: 0.57, 1.55). The authors’ findings are consistent with previous reports of lower acoustic neuroma risk among current cigarette smokers than among never smokers. The absence of an association between snuff use and acoustic neuroma suggests that some constituent of tobacco smoke other than nicotine may confer protection against acoustic neuroma

Neuropsychological Function and Quality of Life after Resection of Suspected Lower-Grade Glioma in the Face Primary Motor Area

The negative side effects of neurosurgical resection of the lower third of the primary motor cortex (M1) are often described as relatively mild. However, detailed descriptions of how these resections affect neurocognitive function, speech, mental health and quality of life (QoL) are sparse. In the present study, seven patients with suspected lower-grade glioma (WHO II-III) in the inferior M1 were assessed for facial motor function, cognitive function, anxiety and QoL before and after awake surgical resections. The main finding was that after surgery, six of the seven patients experienced a mild facial motor dysfunction, mainly affecting the mouth, tongue and throat. At the group level, we were also able to observe a significant postoperative decline in maximum verbal speed, whereas no negative effects on measures of word production (i.e., verbal fluency) were seen. Self-reported QoL data suggest that some patients experienced increased social isolation postoperatively but do not lend support to the interpretation that this was caused by direct neurological side effects of the surgery. The results appear to support the general notion that awake surgery in the lower M1 can be performed safely and with postoperative deficits that are most often perceived by the patient as tolerable

The creation of protection and hope in patients with malignant brain tumours

The malignant brain tumour disease condenses much of the anguish of cancer diseases. The brain is a vital and delicate organ, and the prognosis is generally unfavourable. The patient is exposed and has to rely on cognitive manoeuvres to manage the mental stress. The purpose of this study was to generate new insights into how the patient constructs a new sense of reality when confronted with the malignant brain tumour diagnosis. Within grounded theory methodology, 30 patients with malignant gliomas were interviewed twice, in direct connection with diagnosis, surgery and radiotherapy. In addition, their partners were interviewed, and quantitative instruments (SMMSE, RDCQ) were used as additional references for assessing the patients cognitively and emotionally. Eleven patients were excluded from the final analysis because of cognitive impairment or personality change. Most of the patients were aware of the fact that the brain tumour exposed them to grave danger, but they were also able to use various cognitive manoeuvres to create protection and hope. This process originated from different sources: the body; helpful relations; cognitive schemata; and the handling of information. The importance of the body to raise hope is emphasized. In the discussion we consider this process as an expression of how the patient brings together reality and hope, thus creating her/his own illusion. These findings are also related to adjacent psychoanalytic theory, proposing a theoretical reference with clinical implications when discussing 'What to tell cancer patients'.coping defence denial glioma hope quality of life

Neuropsychological Function and Quality of Life after Resection of Suspected Lower-Grade Glioma in the Face Primary Motor Area

The negative side effects of neurosurgical resection of the lower third of the primary motor cortex (M1) are often described as relatively mild. However, detailed descriptions of how these resections affect neurocognitive function, speech, mental health and quality of life (QoL) are sparse. In the present study, seven patients with suspected lower-grade glioma (WHO II-III) in the inferior M1 were assessed for facial motor function, cognitive function, anxiety and QoL before and after awake surgical resections. The main finding was that after surgery, six of the seven patients experienced a mild facial motor dysfunction, mainly affecting the mouth, tongue and throat. At the group level, we were also able to observe a significant postoperative decline in maximum verbal speed, whereas no negative effects on measures of word production (i.e., verbal fluency) were seen. Self-reported QoL data suggest that some patients experienced increased social isolation postoperatively but do not lend support to the interpretation that this was caused by direct neurological side effects of the surgery. The results appear to support the general notion that awake surgery in the lower M1 can be performed safely and with postoperative deficits that are most often perceived by the patient as tolerable

Intrathecal treatment trial of rituximab in progressive MS : results after a 2-year extension

Objectives To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period. Methods Participants of a 1-year open-label phase 1b study of IT delivered rituximab to patients with PMS were offered extended treatment with follow-up for an additional 2 years. During the extension phase, treatment with 25 mg rituximab was administered every 6 months via a subcutaneous Ommaya reservoir connected to the right frontal horn with a ventricular catheter. Results Mild to moderate vertigo and nausea occurred in 4 out of 14 participants as temporary adverse events associated with IT rituximab infusion. During the entire 3-year period, two cases of low-virulent bacterial meningitis occurred, which were successfully treated. Walking speed deteriorated significantly during the study. Conclusions IT administration of rituximab via a ventricular catheter was well tolerated. Considering the meningitis cases, the risk of infection was not negligible. The continued loss of walking speed indicates that IT rituximab was not able to stop disease progression. Classification of evidence This study provides class IV evidence that intraventricularly administered rituximab in progressive MS is associated with a risk for bacterial meningitis and does not halt disease progression

How was life after treatment of a malignant brain tumour?

The malignant glioma is a severe disease with an unfavourable prognosis. Aside from a few case studies, the knowledge of the victimised patients' lives from diagnosis to death is mainly restricted to studies assessing functional status and rating quality of life by means of questionnaires. From a clinician's perspective this knowledge is not sufficient. By introducing the concepts 'time of everyday life' and 'time of disease', the purpose of this paper is to supplement with descriptive knowledge of clinical value. Twenty-eight patients with malignant gliomas and their spouses were followed during the course of the disease by repeated interviews. The time after treatment was then judged as representing, 'time of everyday life' or 'time of disease'. Life after treatment turned out to be quite varied. To slightly more than a third of the patients', life-continuity was lost, experiencing only 'time of disease'. Among the others who were judged to experience 'time of everyday life' and who were of working age, nearly two-thirds were able to resume work or studies on a part-time basis. In the total sample, the mean 'time of everyday life' turned out to be nearly equal to 'time of disease', 6.1 and 5.4 months, respectively. The findings are illustrated by case descriptions and the conceptualisation of time into 'everyday life' and 'disease' is proposed as meriting further study.Brain tumour Glioma Quality of life Survival

Neuropsychological Function and Quality of Life after Resection of Suspected Lower-Grade Glioma in the FacePrimary Motor Area

The negative side effects of neurosurgical resection of the lower third of the primary motorcortex (M1) are often described as relatively mild. However, detailed descriptions of how theseresections affect neurocognitive function, speech, mental health and quality of life (QoL) are sparse. Inthe present study, seven patients with suspected lower-grade glioma (WHO II-III) in the inferior M1were assessed for facial motor function, cognitive function, anxiety and QoL before and after awakesurgical resections. The main finding was that after surgery, six of the seven patients experienced amild facial motor dysfunction, mainly affecting the mouth, tongue and throat. At the group level,we were also able to observe a significant postoperative decline in maximum verbal speed, whereasno negative effects on measures of word production (i.e., verbal fluency) were seen. Self-reportedQoL data suggest that some patients experienced increased social isolation postoperatively but donot lend support to the interpretation that this was caused by direct neurological side effects of thesurgery. The results appear to support the general notion that awake surgery in the lower M1 canbe performed safely and with postoperative deficits that are most often perceived by the patient astolerable