Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with ...quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure.
Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data.
Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen.
The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients.
Purpose
This study aimed to detect age-related brain metabolic and microstructural changes in healthy human brains by the use of whole-brain proton magnetic resonance spectroscopic imaging (
1
...H‑MRSI) and quantitative MR imaging (qMRI).
Methods
In this study, 60 healthy participants with evenly distributed ages (between 21 and 69 years) and sex underwent MRI examinations at 3T including whole-brain
1
H‑MRSI. The concentrations of the metabolites N‑acetylaspartate (NAA), choline-containing compounds (Cho), total creatine and phosphocreatine (tCr), glutamine and glutamate (Glx), and myo-inositol (mI), as well as the brain relaxation times T2, T2’ and T1 were measured in 12 regions of interest (ROI) in each hemisphere. Correlations between measured parameters and age were estimated with linear regression analysis and Pearsonʼs correlation test.
Results
Significant age-related changes of brain regional metabolite concentrations and tissue relaxation times were found: NAA decreased in eight of twelve ROIs, Cho increased in three ROIs, tCr in four ROIs, and mI in three ROIs. Glx displayed a significant decrease in one ROI and an increase in another ROI. T1 increased in four ROIs and T2 in one ROI, while T2’ decreased in two ROIs. A negative correlation of tCr concentrations with T2’ relaxation time was found in one ROI as well as the positive correlations of age-related T1 relaxation time with concentrations of tCr, mI, Glx and Cho in another ROI.
Conclusion
Normal aging in human brain is associated with coexistent brain regional metabolic alterations and microstructural changes, which may be related to age-related decline in cognitive, affective and psychomotor domains of life in the older population.
Background and Purpose: Patients with spinal muscular atrophy (SMA) require repeated CT-guided lumbar puncture for cerebrospinal fluid analysis and intrathecal injection of nusinersen. We analysed ...the radiation exposure of 3 different CT systems used in our patients. Methods: Retrospective evaluation of all CT-controlled lumbar punctures in patients with SMA since 11/2017. For each intervention, the number of scans as well as CTDI and DLP values were recorded separately for diagnostics and puncture. Results: 110 CT-guided punctures, 59 on scanner A, 19 on B and 32 on C were successfully performed in 20 patients aged 11 to 65 years. The number of acquisitions per treatment was between 1 and 20, on average 4.7. With system C all cases were below the national diagnostic reference values (BfS) of the bony lumbar spine, they were exceeded with device A in 4/59 and B in 2/19 cases. The mean values of CTDI and DLP were 6.2 mGy-cm and 71.2 mGy-cm for diagnosis and 6.9 mGy-cm and 46.7 mGy for needle puncture, respectively. Interventional radiation exposure was lowest for CT-system C with CTDI and DLP values of 1.2 mGy-cm and 12.1 mGy. Conclusion: The device performance contributes significantly to radiation exposure in CT-supported lumbar punctures of SMA patients. The radiation exposure of the most modern scanner is lower than the nation diagnostic reference values in all cases and results in the lowest amount of radiation exposure for needle-guidance.
Einleitung: Zur Erkennung von metabolischen Veranderungen bei Krankheitsbildern sind Referenzdatensatze erforderlich. Wir haben eine 31P Magnet Resonanz Spektroskopie (31P-MRS) Studie an gesunden ...Probanden durchgefuhrt, um eine mogliche altersabhangige Veranderung der Phosphor Metaboliten im Gehirn festzustellen. Methode: 63 gesunde Probanden mit gleichverteiltem Alter von 20-70 Jahren (30 Frauen, 33 Manner) wurden mit einer doppelt-abgestimmten 1H/31P Volumen-Kopf-Spule (Rapid Biomedical, Wurzburg) am 3T Verio (Siemens, Erlangen) untersucht. Eine non-localized FID-Sequenz (TR = 2000ms, 64 Akquisitionen, Kippwinkel 50degrees) wurde bei einer Untersuchungszeit von ca. 2.5 Minuten verwendet. Ein Phantom (50mM KH.sub.2PO.sub.4) wurde zur Kalibrierung der Metaboliten Konzentrationen ebenfalls gemessen. Die Auswertung der Daten erfolgt mit dem fur 31P-MRS angepassten Programm LCModel 1,2. Damit wurden die Konzentrationen folgender Metaboliten bestimmt: Adenosintriphosphat ATP, Phosphocreatin PCr, Phosphoethanolamin PE, Phosphocholin PCho, Glycerylphosphorylcholin GPC, Glycerylphosphorylethanolamin GPE, anorganisches Phosphat Pi und Nicotinamid-Adenin-Dinukleotid NAD. Mittels zweiseitiger T-Tests wurden mogliche Datenunterschiede zwischen weiblichen und mannlichen Probanden uberpruft. Eine lineare Regressionsanalyse (alpha = 0.05) wurde verwendet, um eine Korrelation der Metaboliten Konzentrationen zum Alter zu untersuchen. Ergebnisse: Die Metaboliten PE, PCho und GPC zeigten signifikante Geschlechtsunterschiede, sodass diese geschlechtlich separat analysiert werden mussten. Die lineare Regressionsanalyse ergab, dass ATP und PE (fur beide Geschlechtergruppen) mit dem Alter signifikant sinkt (Details in Abbildung 1). Fazit: Die gemessenen Phosphor Metaboliten zeigen zum Teil geschlechts- und altersbedingte Unterschiede. Insbesondere ATP reduziert sich mit zunehmendem Alter, was auf eine Veranderung der mitochondrialen Funktion 3 oder auf eine Reduktion des Hirnvolumens hindeuten kann. Die gemessenen Metabolit Werte konnen somit differenziert als Referenzwerte dienen, um pathologisch auftretende Veranderungen des Hirnstoffwechsels bei Patienten zu identifizieren.
The polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) has been shown to support dynamic changes underlying peripheral nerve regeneration. Using transgenic mice expressing ...polysialyltransferase ST8SiaIV under control of a glial-specific (proteolipid protein, PLP) promoter (PLP-ST8SiaIV-transgenic mice), we tested the hypothesis that permanent synthesis of PSA in Schwann cells impairs functional recovery of lesioned peripheral nerves. After sciatic nerve crush, histomorphometric analyses demonstrated impaired remyelination of regenerated axons at the lesion site and in target tissue of PLP-ST8SiaIV-transgenic mice, though the number and size of regenerating unmyelinated axons were not changed. This was accompanied by slower mechanosensory recovery in PLP-ST8SiaIV-transgenic mice. However, the proportion of successfully mono-(re)innervated motor endplates in the foot pad muscle was significantly increased in PLP-ST8SiaIV-transgenic mice when compared with wild-type littermates, suggesting that long-term increase in PSA levels in regenerating nerves may favor selective motor target reinnervation. The combined negative and positive effects of a continuous polysialyltransferase overexpression observed during peripheral nerve regeneration suggest that an optimized time- and differentiation-dependent control of polysialyltransferase expression in Schwann cells may further improve recovery after peripheral nerves injury.
PolySia, the most striking post-translational modification of the neural cell adhesion molecule, is down-regulated during postnatal development. After peripheral nerve lesion, polySia is located on ...neuronal and glial cells normally not synthesizing polySia. However, structural consequences of reduced polySia content for peripheral nerve regeneration have not yet been clear. Furthermore, the contribution of sialyltransferases ST8SiaII and ST8SiaIV for the up-regulation of polySia has not been studied so far. In order to investigate the impact of polySia on regeneration processes of myelinated axons, we examined mouse mutants retaining only one functional sialyltransferase allele. In the absence of ST8SiaII, quantification of myelinated axons revealed a significant decrease in number and size of regenerated fibers without impairment of remyelination. In contrast, St8SiaIV deficiency resulted in increased fiber outgrowth and axonal maturation. Western blot analysis demonstrated that both ST8SiaII and St8SiaIV direct up-regulation of polySia. Cell-specific induction of polySia in myelinating Schwann cells and on regenerated axons in the presence of ST8SiaIV, but not ST8SiaII, indicates that not only the amount of polySia but also its cellular localization has a high impact on the regeneration progress of peripheral nerves.
Herpes simplex virus type 2 (HSV-2) can cause radiculo-myelitis as a neurological manifestation. We report a case of ongoing HSV-2 DNA positivity in the cerebrospinal fluid (CSF) of at least eight ...weeks under antiviral therapy with acyclovir in a highly immunocompromised hemato-oncologic patient with HSV-2-associated radiculitis. Upon admission, the patient presented with pain, leg paresis, and urinary incontinence, as well as pleocytosis in the CSF. Quantitative real-time PCR of the CSF at day 3 after admission revealed HSV-2 with a concentration of 2.0×10(5) copies/ml and treatment with acyclovir intravenously and prednisolone by mouth was started. Clinical symptoms resolved almost completely after approximately 3 weeks of antiviral therapy. However, CSF samples of day 12, 19, 26, 33, 39, 48 and 54 after admission showed a slow decline of HSV-2 DNA concentrations. HSV-2 DNA was still detectable (1.6×10(4) copies/ml) at day 54 after admission. Genotypic resistance testing showed, as far as available, no mutations indicative for acyclovir resistance. Since an increasing specific antibody index for HSV was observed, we speculate that the prolonged detectability of HSV-2 DNA in the CSF might not necessarily indicate ongoing viral replication but neutralized virus. Other hypotheses and the consequences on treatment are discussed. To our knowledge this is the first report about the long-term viral load kinetics of HSV-2 in the CSF of a patient with radiculitis under antiviral therapy, highlighting the need for further studies on HSV DNA kinetics in the CSF and their significance for an appropriate antiviral treatment.
Ziel: Untersuchung der Einflusse des Alterns auf das menschliche Gehirn mittels quantitativer MRT-Messungen. Methoden: 29 Frauen und 33 Manner (22-68 Jahre) wurden nach Ausschluss ...neurologisch-psychischer Alterationen an einem 3 T-MRT untersucht. Aus der MRT-Daten wurden qMRI-Maps der Parameter T1, T2, relative Protonendichte (PD), T2*, Magnitude (Mag) sowie Phase (Pha) der sWI erstellt. Die Werte der jeweiligen Parameter wurden an 16 ROIs je Hemisphare gemessen: WM frontal (fWM), parietal (pWM), hand-knop (HN), Centrum semiovale (CSO), Genu (gcc) und splenium (scc) des corpus callosum, GM occipital (oGM), Basalganglien (cN, Pal, Put), Thalamus (Thal), Hirnstamm ventral (BSV), dorsal (BSD) und Kleinhirn-GM (cbl1, cbl2) sowie -WM (cblWM). Korrelationen von Alter und qMRI-Parametern wurden durch den Pearsons Koeffizient erfasst, die geschlechtsspezifischen Effekte mittels t-Test ausgewertet. Ergebnisse: Geschlechtsspezifische Unterschiede wurden in T2* beobachtet: Frauen zeigten im Vergleich zu Mannern niedrigere T2* in Bs, cbl1, cbl2 und hohere T2* im csO (~ 3 ms, p < 0,03). Mag zeigte die hochsten Alterskorrelationen, abnehmend in Bsv, gcc, scc, cN, Pal, Put und Thal (r = -0,7 bis--0,3, p < 0,02); T2* zeigte alterungsbedingte Abnahmen im gCC, HN, CN, Put, oGM (r = -0,7 bis-0,3, p < 0,04) und PD im BSd, gCC, HN, Thal (r = - 0,5 bis-0,3, p < 0,03); T2 zeigte eine altersabhangige Zunahme im gcc (r = 0,4, p = 0,001) und eine Abnahme im scc (r = -0,6, p = 0,0001) und cN (r = - 0,3, p = 0,02). Fazit: qMRT kann cerebrale Alterungseffekte aufdecken, die mit herkommlichen MRT-Verfahren nicht darstellbar sind. Die ROIs gcc und cN erscheinen am sensibelsten auf Alterungsprozesse zu reagieren, wahrend Mag der empfindlichste Parameter zu sein scheint.
During the COVID-19 pandemic, vaccination is the most important countermeasure. Pharmacovigilance concerns however emerged with very rare, but potentially disastrous thrombotic complications ...following vaccination with ChAdOx1. Platelet factor-4 antibody mediated vaccine-induced immune thrombotic thrombocytopenia (VITT) was described as an underlying mechanism of these thrombotic events. Recent work moreover suggests that mechanisms of immunothrombosis including neutrophil extracellular trap (NET) formation might be critical for thrombogenesis during VITT. In this study, we investigated blood and thrombus specimens of a female patient who suffered severe stroke due to VITT after vaccination with ChAdOx1 in comparison to 13 control stroke patients with similar clinical characteristics. We analyzed cerebral thrombi using histological examination, staining of complement factors, NET-markers, DNase and LL-37. In blood samples at the hyper-acute phase of stroke and 7 days later, we determined cell-free DNA, myeloperoxidase-histone complexes, DNase activity, myeloperoxidase activity, LL-37 and inflammatory cytokines. NET markers were identified in thrombi of all patients. Interestingly, the thrombus of the VITT-patient exclusively revealed complement factors and high amounts of DNase and LL-37. High DNase activity was also measured in blood, implying a disturbed NET-regulation. Furthermore, serum of the VITT-patient inhibited reactive oxygen species-dependent NET-release by phorbol-myristate-acetate to a lesser degree compared to controls, indicating either less efficient NET-inhibition or enhanced NET-induction in the blood of the VITT-patient. Additionally, the changes in specific cytokines over time were emphasized in the VITT-patient as well. In conclusion, insufficient resolution of NETs, e.g. by endogenous DNases or protection of NETs against degradation by embedded factors like the antimicrobial peptide LL-37 might thus be an important factor in the pathology of VITT besides increased NET-formation. On the basis of these findings, we discuss the potential implications of the mechanisms of disturbed NETs-degradation for diagnostic and therapeutic approaches in VITT-related thrombogenesis, other auto-immune disorders and beyond.
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