Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis.

BACKGROUND: Iron rims (IRs) surrounding white matter lesions (WMLs) are suggested to predict a more severe disease course. Only small longitudinal cohorts of patients with and without iron rim lesions (IRLs) have been reported so far. OBJECTIVE: To assess whether the presence and number of IRLs in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) are associated with long-term disability or progressive disease. METHODS: Ninety-one CIS/MS patients were recruited between 2008 and 2013 and scanned with 7 T magnetic resonance imaging (MRI). Expanded Disability Status Scale (EDSS) was used to calculate Age-related Multiple Sclerosis Severity Score (ARMSS) at the time of scan and at the latest clinical follow-up after 9 years. WMLs were assessed for the presence of IRL using Susceptibility weighted imaging (SWI)-filtered phase images. RESULTS: In all, 132 IRLs were detected in 42 patients (46%); 9% of WMLs had IRs; 54% of the cohort had no rims, 30% had 1-3 rims and 16% had ⩾4. Patients with IRL had a higher EDSS and ARMSS. Presence of IRL was also a predictor of long-term disability, especially in patients with ⩾4 IRLs. IRLs have a greater impact on disability compared to the WML number and volume. CONCLUSION: The presence and number of perilesional IR on MRI hold prognostic value for long-term clinical disability in MS.

C-C Chemokine Receptor 7 in Cancer.

C-C chemokine receptor 7 (CCR7) was one of the first two chemokine receptors that were found to be upregulated in breast cancers. Chemokine receptors promote chemotaxis of cells and tissue organization. Since under homeostatic conditions, CCR7 promotes migration of immune cells to lymph nodes, questions immediately arose regarding the ability of CCR7 to direct migration of cancer cells to lymph nodes. The literature since 2000 was examined to determine to what extent the expression of CCR7 in malignant tumors promoted migration to the lymph nodes. The data indicated that in different cancers, CCR7 plays distinct roles in directing cells to lymph nodes, the skin or to the central nervous system. In certain tumors, it may even serve a protective role. Future studies should focus on defining mechanisms that differentially regulate the unfavorable or beneficial role that CCR7 plays in cancer pathophysiology, to be able to improve outcomes in patients who harbor CCR7-positive cancers.

Mild traumatic brain injury impairs the coordination of intrinsic and motor-related neural dynamics.

Mild traumatic brain injury (mTBI) poses a considerable burden on healthcare systems. Whilst most patients recover quickly, a significant number suffer from sequelae that are not accompanied by measurable structural damage. Understanding the neural underpinnings of these debilitating effects and developing a means to detect injury, would address an important unmet clinical need. It could inform interventions and help predict prognosis. Magnetoencephalography (MEG) affords excellent sensitivity in probing neural function and presents significant promise for assessing mTBI, with abnormal neural oscillations being a potential specific biomarker. However, growing evidence suggests that neural dynamics are (at least in part) driven by transient, pan-spectral bursting and in this paper, we employ this model to investigate mTBI. We applied a Hidden Markov Model to MEG data recorded during resting state and a motor task and show that previous findings of diminished intrinsic beta amplitude in individuals with mTBI are largely due to the reduced beta band spectral content of bursts, and that diminished beta connectivity results from a loss in the temporal coincidence of burst states. In a motor task, mTBI results in diminished burst amplitude, altered modulation of burst probability during movement, and a loss in connectivity in motor networks. These results suggest that, mechanistically, mTBI disrupts the structural framework underlying neural synchrony, which impairs network function. Whilst the damage may be too subtle for structural imaging to see, the functional consequences are detectable and persist after injury. Our work shows that mTBI impairs the dynamic coordination of neural network activity and proposes a potent new method for understanding mTBI.

Magnetoencephalography abnormalities in adult mild traumatic brain injury: A systematic review.

BACKGROUND: The global incidence of traumatic brain injuries is rising, with at least 80% being classified as mild. These mild injuries are not visible on routine clinical imaging. The potential clinical role of a specific imaging biomarker be it diagnostic, prognostic or directing and monitoring progress of personalised treatment and rehabilitation has driven the exploration of several new neuroimaging modalities. This systematic review examined the evidence for magnetoencephalography (MEG) to provide an imaging biomarker in mild traumatic brain injury (mTBI). METHODS: Our review was prospectively registered on PROSPERO: CRD42019151387. We searched EMBASE, MEDLINE, trial registers, PsycINFO, Cochrane Library and conference abstracts and identified 37 papers describing MEG changes in mTBI eligible for inclusion. Since meta-analysis was not possible, based on the heterogeneity of reported outcomes, we provide a narrative synthesis of results. RESULTS: The two most promising MEG biomarkers are excess resting state low frequency power, and widespread connectivity changes in all frequency bands. These may represent biomarkers with potential for diagnostic application, which reflect time sensitive changes, or may be capable of offering clinically relevant prognostic information. In addition, the rich data that MEG produces are well-suited to new methods of machine learning analysis, which is now being actively explored. INTERPRETATION: MEG reveals several promising biomarkers, in the absence of structural abnormalities demonstrable with either computerised tomography or magnetic resonance imaging. This review has not identified sufficient evidence to support routine clinical use of MEG in mTBI currently. However, verifying MEG's potential would help meet an urgent clinical need within civilian, sports and military medicine.

Single Test to ARrive at Multiple Sclerosis (STAR-MS) diagnosis: A prospective pilot study assessing the accuracy of the central vein sign in predicting multiple sclerosis in cases of diagnostic uncertainty.

BACKGROUND: Misdiagnosis is common in multiple sclerosis (MS) as a proportion of patients present with atypical clinical/magnetic resonance imaging (MRI) findings. The central vein sign has the potential to be a non-invasive, MS-specific biomarker. OBJECTIVE: To test the accuracy of the central vein sign in predicting a diagnosis of MS in patients with diagnostic uncertainty at disease presentation using T2*-weighted, 3 T MRI. METHODS: In this prospective pilot study, we recruited individuals with symptoms unusual for MS but with brain MRI consistent with the disease, and those with a typical clinical presentation of MS whose MRI did not suggest MS. We calculated the proportion of lesions with central veins for each patient and compared the results to the eventual clinical diagnoses. The optimal central vein threshold for diagnosis was established. RESULTS: Thirty-eight patients were scanned, 35 of whom have received a clinical diagnosis. Median percentage of lesions with central veins was 51% in MS and 28% in non-MS. A threshold of 40.7% lesions with central veins resulted in 100% sensitivity and 73.9% specificity. CONCLUSION: The central vein sign assessed with a clinically available T2* scan can successfully diagnose MS in cases of diagnostic uncertainty. The central vein sign should be considered as a diagnostic biomarker in MS.

Full genome re-sequencing reveals a novel circadian clock mutation in Arabidopsis.

Map based cloning in Arabidopsis thaliana can be a difficult and time-consuming process, specifically if the phenotype is subtle and scoring labour intensive. Here, we have re-sequenced the 120-Mb genome of a novel Arabidopsis clock mutant early bird (ebi-1) in Wassilewskija (Ws-2). We demonstrate the utility of sequencing a backcrossed line in limiting the number of SNPs considered. We identify a SNP in the gene AtNFXL-2 as the likely cause of the ebi-1 phenotype.