Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system. Increasing evidence indicates additional peripheral nerve involvement in early and chronic disease stages. To ...investigate the evolution of peripheral nerve changes in patients first diagnosed with MS using quantitative MR neurography.
This prospective study included 19 patients with newly diagnosed MS according to the revised McDonald criteria (16 female, mean 30.2 ± 7.1 years) and 19 age-/sex-matched healthy volunteers. High-resolution 3 T MR neurography of the sciatic nerve using a quantitative T2-relaxometry sequence was performed, which yielded the biomarkers of T2 relaxation time (T2app) and proton spin density (PSD). Follow-up scans of patients were performed after median of 12 months (range 7-16). Correlation analyses considered clinical symptoms, intrathecal immunoglobulin synthesis, nerve conduction study, and lesion load on brain and spine MRI.
Patients showed increased T2app and decreased PSD compared to healthy controls at initial diagnosis and follow-up (
< 0.001 each). Compared to the initial scan, T2app further increased in patients at follow-up (
= 0.003). PSD further declined by at least 10% in 9/19 patients and remained stable in another 9/19 patients. Correlation analyses did not yield significant results.
Peripheral nerve involvement in MS appears at initial diagnosis and continues to evolve within 1 year follow-up with individual dynamics. Quantitative MRN provides non-invasive biomarkers to detect and monitor peripheral nerve changes in MS.
Background and Purpose:
To compare safety and efficacy of conscious sedation (CS) vs. general anesthesia (GA) in endovascular stroke treatment (EST) of the posterior circulation (PC).
Methods:
...Retrospective single-center analysis of patients receiving EST for large-vessel occlusion (LVO) in PC between January 2015 and November 2020. Exclusion criteria were severe stroke syndromes (NIHSS > 20), decreased level of consciousness, intubation for transport, and second stroke within 3 months of follow-up. The primary endpoint was a favorable clinical outcome 90 days after stroke onset (mRS 0–2 or 3 if pre-stroke mRS 3). Secondary endpoints were the rate of EST failure and procedural complications.
Results:
Of 111 included patients, 45/111 patients (40.5%) were treated under CS and 60/111 (54.0%) under GA. In 6/111 cases (5.4%), sedation mode was changed from CS to GA during EST. Patients treated under CS showed a lower mRS 90 days after stroke onset mRS, median (IQR): 2.5 (1–4) CS vs. 3 (2–6) GA,
p
= 0.036 and a comparable rate of good outcome good outcome,
n
(%): 19 (42.2) CS vs. 15 (32.6) GA,
p
= 0.311. There was no difference in complication rates during EST (6.7% CS vs. 8.3% GA) or intracranial bleeding in follow-up imaging
n
(%): 4 (8.9) CS vs. 7 (11.7) GA),
p
= 0.705. The rate of successful target vessel recanalization did not differ (84.4% CS vs. 85.0 % GA).
Conclusions:
In this retrospective study, EST of the posterior circulation under conscious sedation was for eligible patients comparably safe and effective to patients treated under general anesthesia.
Background
Magnetic resonance imaging is essential for monitoring people with multiple sclerosis, but the diagnostic value of gadolinium contrast administration in spine magnetic resonance imaging is ...unclear.
Objective
To assess the diagnostic value of gadolinium contrast administration in spine magnetic resonance imaging follow-up examinations and identify imaging markers correlating with lesion enhancement.
Methods
A total of 65 multiple sclerosis patients with at least 2 spinal magnetic resonance imaging follow-up examinations were included. Spine magnetic resonance imaging was performed at 3 Tesla with a standardized protocol (sagittal and axial T2-weighted turbo spin echo and T1-weighted post-contrast sequences). T2 lesion load and enhancing lesions were assessed by two independent neuroradiologists for lesion size, localization, and T2 signal ratio (T2 signallesion/T2 signalnormal appearing spinal cord).
Results
A total of 68 new spinal T2 lesions and 20 new contrast-enhancing lesions developed during follow-up. All enhancing lesions had a discernable correlate as a new T2 lesion. Lesion enhancement correlated with a higher T2 signal ratio compared to non-enhancing lesions (T2 signal ratio: 2.0 ± 0.4 vs. 1.4 ± 0.2, ***p < 0.001). Receiver operating characteristics analysis showed an optimal cutoff value of signal ratio 1.78 to predict lesion enhancement (82% sensitivity and 97% specificity).
Conclusion
Gadolinium contrast administration is dispensable in follow-up spine magnetic resonance imaging if no new T2 lesions are present. Probability of enhancement correlates with the T2 signal ratio.
Background and purpose
Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS). However, there is increasing evidence of peripheral nerve involvement. This study aims ...to characterize the pattern of peripheral nerve changes in patients with newly diagnosed MS using quantitative magnetic resonance (MR) neurography.
Methods
In this prospective study, 25 patients first diagnosed with MS according to the revised McDonald criteria (16 female, mean age = 32.8 ± 10.6 years) and 14 healthy controls were examined with high‐resolution 3‐T MR neurography of the sciatic nerve using diffusion kurtosis imaging (DKI; 20 diffusional directions, b = 0, 700, 1200 s/mm2) and magnetization transfer imaging (MTI). In total, 15 quantitative MR biomarkers were analyzed and correlated with clinical symptoms, intrathecal immunoglobulin synthesis, electrophysiology, and lesion load on brain and spine MR imaging.
Results
Patients showed decreased fractional anisotropy (mean = 0.51 ± 0.04 vs. 0.56 ± 0.03, p < 0.001), extra‐axonal tortuosity (mean = 2.32 ± 0.17 vs. 2.49 ± 0.17, p = 0.008), and radial kurtosis (mean = 1.40 ± 0.23 vs. 1.62 ± 0.23, p = 0.014) and higher radial diffusivity (mean = 1.09 ∙ 10−3 mm2/s ± 0.16 vs. 0.98 ± 0.11 ∙ 10−3 mm2/s, p = 0.036) than controls. Groups did not differ in MTI. No significant association was found between MR neurography markers and clinical/laboratory parameters or CNS lesion load.
Conclusions
This study provides further evidence of peripheral nerve involvement in MS already at initial diagnosis. The characteristic pattern of DKI parameters indicates predominant demyelination and suggests a primary coaffection of the peripheral nervous system in MS. This first human study using DKI for peripheral nerves shows its potential and clinical feasibility in providing novel biomarkers.
•Cancer patients show significant balance deficits following neurotoxic chemotherapy•Balance deficits are most apparent under visual deprivation•Balance deficits are most strongly associated with ...nerve conduction velocity
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect deriving from neurotoxic chemotherapeutic agents. The underlying nerve injury can affect proprioception causing impaired postural control, gait difficulties and a higher risk of falling. Overall, the symptoms and functional limitations negatively affect patients’ independence and quality of life.
Our objective was to analyze postural control in cancer patients before and after neurotoxic chemotherapy and to compare these data to healthy controls.
Participants were 35 cancer patients (PAT) and 35 healthy, one-to-one gender, age, height, and weight matched controls (HMC). Postural control of HMC was tested once, whereas PAT were tested prior to (PATpre) and three weeks after completion of neurotoxic chemotherapy (PATpost). Temporal, spatial and frequency domain measures of the center of pressure (COP) were calculated using a force plate. The following balance conditions were analyzed: bipedal stance with open (BPEO) and closed eyes (BPEC), semi-tandem (STEO, STEC) and monopedal stance (MPEO). CIPN was assessed clinically (Total Neuropathy Score) and via questionnaire. Time and group differences were determined by using Wilcoxon-signed-rank tests. Spearman correlation was applied to analyze associations between severity of CIPN and postural control.
PATpost showed significantly increased temporal and spatial measures of the COP (p < .05) – both after neurotoxic chemotherapy (PATpre–PATpost) and in comparison to HMC. Withdrawal of visual control resulted in greater temporal and spatial COP displacements in PATpost than in the comparative groups (PATpre, HMC). Correlation analyzes revealed moderate associations of COP measures with clinical CIPN measures and low to none for the questionnaires.
Three weeks after completion of neurotoxic chemotherapy, PATpost showed significant balance deficits compared to PATpre and HMC. Especially the deficits in the standing conditions with closed eyes may indicate an impaired proprioception. This hypothesis is supported by the finding that stronger CIPN symptoms were associated with poorer postural control. However, future studies need to take further influencing factors on postural control into account (e.g. strength) in order to generate efficacious rehabilitation measures.
The aim of this study was to assess peripheral nerve involvement in patients with multiple sclerosis (MS) at first clinical presentation using quantitative magnetic resonance (MR) neurography in ...correlation with clinical, laboratory, electrophysiological, and central nervous MR imaging data.
In this prospective monocentric study, 30 patients first diagnosed with MS according to the McDonald criteria (19 women; mean age, 32.4 ± 8.8 years) and 30 age- and sex-matched healthy volunteers were examined with high-resolution 3 T MR neurography using a dual-echo T2-relaxometry sequence covering the tibial and peroneal nerves from proximal thigh to distal calf. Magnetic resonance biomarkers of T2 relaxation time (T2 app ), proton spin density (PSD), and nerve cross-sectional area (CSA) were correlated with clinical symptoms, intrathecal immunoglobulin (Ig) synthesis, nerve conduction study, and lesion load on brain and spine MR imaging. The diagnostic accuracy of MR biomarkers was assessed using receiver-operating characteristic curves.
Diffuse nerve changes were detected along the tibial and peroneal nerves in MS patients, who showed decreased PSD ( P < 0.001), increased T2 app ( P < 0.001), and smaller tibial nerve CSA ( P < 0.001) compared with healthy subjects. Tibial PSD was identified as best parameter separating patients from controls (area under the curve = 0.876). Intrathecal IgG and IgM synthesis correlated with PSD values ( r = -0.44, P = 0.016, and r = -0.42, P = 0.022). Contrast-enhancement of brain or spine lesions was related to larger tibial and peroneal CSA ( P < 0.001, P = 0.033). Abnormal electrophysiology correlated with higher tibial and peroneal T2 app ( P < 0.001 and P = 0.033), lower tibial and peroneal PSD ( P = 0.018 and P = 0.002), and smaller peroneal CSA ( P < 0.001).
Quantitative MR neurography reveals peripheral nerve changes in patients with initial diagnosis of MS. Correlation of imaging findings with intrathecal immunoglobulin synthesis may indicate a primary coaffection of the peripheral nervous system in MS.
Background
Optimal blood pressure (BP) management during endovascular stroke treatment in patients with large-vessel occlusion is not well established. We aimed to investigate associations of BP ...during different phases of endovascular therapy with reperfusion and functional outcome.
Methods
We performed a post hoc analysis of a single-center prospective study that evaluated a new simplified procedural sedation standard during endovascular therapy (Keep Evaluating Protocol Simplification in Managing Periinterventional Light Sedation for Endovascular Stroke Treatment). BP during endovascular therapy in patients was managed according to protocol. Data from four different phases (baseline, pre-recanalization, post recanalization, and post intervention) were obtained, and mean BP values, as well as changes in BP between different phases and reductions in systolic BP (SBP) and mean arterial pressure (MAP) from baseline to pre-recanalization, were used as exposure variables. The main outcome was a modified Rankin Scale score of 0–2 three months after admission. Secondary outcomes were successful reperfusion and change in the National Institutes of Health Stroke Scale score after 24 h. Multivariable linear and logistic regression models were used for statistical analysis.
Results
Functional outcomes were analyzed in 139 patients with successful reperfusion (defined as thrombolysis in cerebral infarction grade 2b–3). The mean (standard deviation) age was 76 (10.9) years, the mean (standard deviation) National Institutes of Health Stroke Scale score was 14.3 (7.5), and 70 (43.5%) patients had a left-sided vessel occlusion. Favorable functional outcome (modified Rankin Scale score 0–2) was less likely with every 10-mm Hg increase in baseline (odds ratio OR 0.76,
P
= 0.04) and pre-recanalization (OR 0.65,
P
= 0.011) SBP. This was also found for baseline (OR 0.76,
P
= 0.05) and pre-recanalization MAP (OR 0.66,
P
= 0.03). The maximum Youden index in a receiver operating characteristics analysis revealed an SBP of 163 mm Hg and MAP of 117 mm Hg as discriminatory thresholds during the pre-recanalization phase to predict functional outcome.
Conclusions
In our protocol-based setting, intraprocedural pre-recanalization BP reductions during endovascular therapy were not associated with functional outcome. However, higher intraprocedural pre-recanalization SBP and MAP were associated with worse functional outcome. Prospective randomized controlled studies are needed to determine whether BP is a feasible treatment target for the modification of outcomes.
Aim
Genetic connectivity and diversity are key components of species' resilience to environmental change. However, the specific factors shaping species' resilience are poorly understood. We here aim ...to strengthen our understanding of resilience in two butterfly species, by identifying regions of high genetic diversity and barriers to dispersal.
Location
European Alps.
Taxon
Copper butterflies (Lycaena spp.).
Methods
We sampled 21 Lycaena hippothoe and 14 L. virgaureae populations with 18 individuals each in the European Alps. Using 14 and 9 microsatellite markers, respectively, we analysed genetic diversity and population structure (using arlequin, genalex, structure and snmf). We analysed spatial patterns of gene flow and genetic diversity (using an estimated effective migration surface), population demographic history and effective population size (diyabc), habitat suitability (maxent), and isolation by distance, and with resistance (genalex, circuitscape).
Results
We found higher genetic diversity and a more pronounced genetic structure in L. hippothoe than in L. virgaureae. Both species displayed a major genetic barrier in the central Alps. Western and eastern populations showed the highest genetic diversity in L. hippothoe, but central ones in L. virgaureae. Populations of both species were structured by geodetic distance, and minimum and maximum altitude.
Main Conclusions
The population genetic structure of both Copper butterflies seemed to be strongly affected by population history, demography and geographic features. Valleys and high mountain ridges seem to comprise major dispersal barriers. The high genetic diversity and pronounced population structure found in L. hippothoe seems to be related to a low dispersal ability and closed populations with high local abundances as opposed to L. virgaureae. We suggest that different conservation strategies are needed for these closely related species, focussing on connecting suitable habitats in L. hippothoe and increasing local population sizes in L. virgaureae.
Thesis (MSc)--Stellenbosch University, 2014.
ENGLISH ABSTRACT: Diuraphis noxia (Kurdjumov, Hemiptera, Aphididae) commonly known as the Russian wheat aphid (RWA), is a small phloem-feeding pest of ...wheat (Triticum aestivum L). Virulent D. noxia biotypes that are able to feed on previously resistant wheat cultivars continue to develop and therefor the identification of factors contributing to virulence is vital. Since energy metabolism plays a key role in the survival of organisms, genes and processes involved in the production and regulation of energy may be key contributors to virulence: such as mitochondria and the NAD+/NADH that reflects the health and metabolic activities of a cell. The involvement of carotenoids in the generation of energy through a photosynthesis-like process may be an important factor, as well as its contribution to aphid immunity through mediation of oxidative stress. The complete mitochondrial genome of global Diuraphis noxia populations was characterised using Next Generation sequencing, and was found to be 15 721bp in size and consisting of 38 genes typically found within most insects. Single nucleotide polymorphism (SNP) analyses of the genomes of nine populations revealed 125 SNPs in the protein coding genes with the majority of the SNPs occurring in the ND genes, and the least in the ND4L gene. Low SNP variant frequency was found for the atp6 and atp8 genes, which differed from other reports in the Hemiptera. Variable ND5 expression levels were observed among the biotypes, although no correlation was apparent between ND5 expression and the virulence associated with each biotype. Whereas atp6 transcription was higher in the highly virulent biotype (SAM) under normal and stressful conditions in comparison to the least virulent biotype (SA1). A significantly higher NAD+/NADH ratio was also observed for the SAM biotype under stressful conditions in comparison to the lesser virulent biotypes. UPLC-MS analysis did not reveal any lycopene or β-carotene due to low compound concentrations in the extracted samples but various hydrophobic compounds were present in different concentrations among the biotypes. The carotene desaturase expression profile revealed that SA1 had the lowest relative expression of the gene involved in carotenoid products, while SAM had the highest, under normal and stressful conditions. The results indicate that sequence conservation in mitochondrial genes are associated with key energy processes to maintain a state of homeostasis under variable conditions and that the generation of energy is a contributing factor to the virulence development of D. noxia. The results also show that carotenoids may possibly contribute to fitness of D. noxia through reactive oxygen species scavenging or the production of additional energy, but further investigation is needed for confirmation.
AFRIKAANSE OPSOMMING: Diuraphis noxia (Kurdjumov, Hemiptera, Aphididae) algemeen bekend as die Russiese koringluis (RWA), is ‘n klein floëem-voedende pes van koring (Triticum aestivum L). Virulente D. noxia biotipes wat instaat is om op voorheen bestande koring kultivars te voed gaan ontwikkel voortdurend, en daarom is die identifisering van faktore wat kan bydrae tot virulensie so belangrik. Omdat energie-metabolisme ‘n sleutelrol in die oorlewing van organismes speel, kan gene en prosesse wat by die produksie en regulering van energie betrokke is belangrike bydraers tot virulensie lewer: soos onder andere mitokondria en die NAD+/NADH-verhouding wat die gesondheid en metaboliese aktiwiteit van ‘n sel reflekteer. Die betrokkenheid van karotenoïede in die produksie van energie deur 'n fotosintese-verwante proses kan 'n belangrike faktor bydraend tot luis fiksheid wees, asook die bydra daarvan tot plantluis-immuniteit deur bemiddeling van oksidatiewe stres. Die volledige mitochondriale genoom van globale Diuraphis noxia populasies is met behulp van volgende generasie DNA volgordebepaling gekarrakteriseer, en daar is bevind dat dit 15 721 bp in grootte is en uit 38 gene bestaan wat tipies binne insekte voorkom. Enkelnukleotied- polimorfisme (SNP) ontleding van die genome van nege populasies het onthul dat daar 125 SNPs in die proteïen-koderende gene voorkom, met die meerderheid van die SNPs in die ND-gene, en die minste in die ND4L-geen. Lae SNP-frekwensies is gevind vir die atp6- en atp8- gene, wat verskil van verslae oor ander Hemiptera. Veranderlike ND5-uitdrukkingsvlakke onder die biotipes is waargeneem, alhoewel geen korrelasie duidelik was tussen ND5-uitdrukking en die virulensie geassosieer met elke biotipe nie. Die transkripsie van atp6 was hoër in die hoogs virulente biotipe (SAM) onder normale en stresvolle toestande in vergelyking met die minste virulente biotipe (SA1). ‘n Aansienlike hoër NAD+/NADH-verhouding is ook waargeneem vir die SAM-biotipe onder spanningsvolle omstandighede in vergelyking met die minder virulente biotipes. UPLC-MS-analise het geen likopeen of β-karoteen geïdentifiseer nie as gevolg van lae verbinding konsentrasies in die onttrekte monsters, maar verskeie hidrofobiese verbindings was in verskillende konsentrasies tussen die biotipes teenwoordig. Die karoteen desaturase-uitdrukkingsprofiel het aangetoon dat SA1 die laagste relatiewe uitdrukking van gene betrokke by karotenoïed produksie het, terwyl SAM die hoogste relatiewe uitdrukking onder normale en spanningsvolle omstandighede het. Die resultate van die studie dui daarop dat die volgorde bewaring in mitochondriale gene verband hou met die sleutel energie prosesse om 'n toestand van homeostase onder wisselende omstandighede te handhaaf en dat die produksie van energie 'n bydraende faktor tot die ontwikkeling van virulensie in D. noxia is. Die resultate toon ook aan dat karotenoïede moontlik kan bydra tot fiksheid van D. noxia deur reaktiewe suurstofspesies te aas of deur die produksie van addisionele energie, maar verdere ondersoeke word benodig ter bevestiging.
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