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Compression of the trigeminal root entry zone by a blood vessel can cause trigeminal neuralgia (TN). However, a neurovascular conflict does not explain all cases of TN, and TN can exist without a neurovascular contact. A common observation during microvascular decompression surgery to treat TN is arachnoiditis in the region of the trigeminal nerve. Thus, aberrant inflammatory mechanisms may be involved in the pathophysiology of TN but information about the role of inflammation in TN is scarce. We used Proximity Extension Assay technology to analyse the levels of 92 protein biomarkers related to inflammation in lumbar cerebrospinal fluid from patients with TN (n = 27) before and after microvascular decompression compared to individuals without TN. We aimed to analyse the pattern of inflammation-related proteins in order to improve our understanding of the pathophysiology of TN. The main finding was that immunological protein levels in the cerebrospinal fluid from patients with TN decreased after surgery towards levels observed in healthy controls. Two proteins seemed to be of specific interest for TN: TRAIL and TNF-β. Thus, inflammatory activity might be one important mechanism in TN. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short- and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI. [ABSTRACT FROM AUTHOR]

Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I--hemispheric lesions, stage II--corpus callosum lesions, stage III--brainstem lesions, and stage IV--substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years). [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major health and socio-economic problem that affects all societies. This condition results from the application of external physical strength to the brain that leads to transitory or permanent structural and functional impairments. Moreover, TBI is a risk factor for neurodegeneration and can e.g., increase the risk for Parkinson's disease (PD), a late-onset neurodegenerative disorder with loss of dopaminergic neurons in substantia nigra. In this study, we wanted to explore the possible development of PD-related pathology within the context of an experimental model of TBI. Traumatic brain injury was induced in mice by controlled cortical impact. At different time points behavioral tests (open field, elevated plus maze tests, and Barnes maze) were performed: The animals were sacrificed 30 days after the impact and the brains were processed for Western blot and immunohistochemical analyses. Following TBI there was a significant decrease in expression of tyrosine hydroxylase and dopamine transporter in the substantia nigra as well as significant behavioral alterations. In addition, a strong increase in neuroinflammation was evident, as shown by increased levels of cyclooxygenase-2 and inducible nitric oxide synthase as well as IkB-a degradation and nuclear-kB translocation. Moreover, neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, nerve growth factor, and glial cell line-derived neurotrophic factor were decreased 30 days post-TBI. Interestingly, we observed a significant accumulation of a-synuclein in microglia compared to astrocytes. This study suggests that PD-related molecular events can be triggered upon TBI. The biological mechanisms linking brain trauma and neurodegenerative diseases need to be further investigated. [ABSTRACT FROM AUTHOR]

Aims: The locus of the probable cause of trigeminal neuralgia (TN), the neurovascular conflict at the root entry zone, is in a highly interesting region with regard to inflammatory processes. During surgery for TN, arachnoiditis is frequently observed around the trigeminal root. We hypothesize that aberrant inflammatory mechanisms are involved in the pathophysiology of TN and could predispose the individual to develop the disease. However, at date, information about inflammation in TN is lacking. Methods: We analysed the levels of 92 protein biomarkers related to inflammation in serum and cerebrospinal fluid using computational biology to assess if patients with classical TN have a distinct pattern of inflammatory related proteins compared to controls. We invited patients with TN scheduled for surgery with microvascular decompression (MVD) to participate in the study and included 33 patients. From all patients we obtained serum samples the day before surgery and 27 patients also accepted that we collected CSF. Serum collected from TN patients was compared with serum from 22 age- and sex-matched healthy blood donors. The CSF was compared with 28 control samples collected from a different site. Multiplexed proximity extension assay (PEA) was conducted using Proseek Multiplex Inflammation I (Olink Bioscience, Uppsala, Sweden). Data are expressed as Normalized Protein expression (NPX) and used on log2 scale for relative quantification between samples and is not an absolute quantification of protein expression. For statistical analysis, we used a multivariate PLS-DA classification model. The relative importance of protein for discriminating the groups is given by the loadings and variable importance projection (VIP). Proteins with VIPXL.3 are considered important. For each protein, we also tested whether there is a difference between TN patients and controls using linear regression, adjusting for age and gender by using a likelihood ratio test (LRT). The computed p-values were adjusted for multiple tests using Benjamini and Hochberg's method for controlling the false discovery rate (FDR) and FDR q-values are reported. The threshold for significance is set to 10% FDR. Results: A PLS-DA model was computed to distinguish between serum from TN patients and healthy controls. Using ten five-fold cross validations the average error rate was 0.08, meaning that the model can with 92% accuracy predict if a sample belongs to the TN or healthy control group. In serum, seven proteins (VIP>1.3) were increased in TN compared to controls (FGF23, TRAIL, IL-12B, CXCL10, MCP-4, GDNF and CXCL11) and five proteins had decreased levels in TN compared to controls (TGF-alpha, CXCL5, MMP-10, CASP-8 and IL8). In CSF, four proteins (VIP>1.3) were increased in TN (TRAIL, CXCL6, ADA and CST5) and three proteins were decreased (LAP TGF-beta-1, CASP-8 and IL-1...). Four proteins had aberrant levels in both serum and CSF: CASP-8, GDNF, FGF-23 and TRAIL. Serum CASP-8 levels could alone distinguish between TN patients and healthy controls. Conclusions: By using PEA technology we show that levels of protein markers related to inflammation differ significantly between patients with TN and control groups, both in serum and CSF. The most salient result was the low levels of Caspase-8 in patients with TN. Thus, inflammatory mechanisms may be important for the pathophysiology of TN and may predispose individuals to develop the disease. [ABSTRACT FROM AUTHOR]