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ZusammenfassungDer Goldstandard in der Behandlung der Phlebothrombose ist die konservative Therapie mittels Antikoagulation und Kompression. Bei akuten proximalen iliofemoralen Thrombosen mit Beteiligung der Beckenvene muss jedoch hierbei mit einer Inzidenz für das Entstehen eines postthrombotischen Syndroms im Langzeitverlauf von bis zu 70 % gerechnet werden. Zur Prävention eines solchen Folgeschadens rückt neben der selten durchgeführten operativen venösen Thrombektomie in den letzten Jahren zunehmend die interventionelle rekanalisierende Therapie in den Fokus der Behandlungsstrategie. In dieser Übersicht werden die verschiedenen Techniken und aktuellen Entwicklungen dieser Therapie dargestellt und einer kritischen Wertung vor dem Hintergrund der bestehenden Evidenz unterzogen.

Objective: Intrathecal Immunoglobulin M synthesis (IgM Intrathecal Fraction (IF) +) and spinal MRI lesions are both strong independent predictors of higher disease activity and severity in multiple sclerosis (MS). We investigated whether IgM IF + is associated with spinal cord manifestation and higher neuroaxonal damage in early MS. Methods: In 122 patients with a first demyelinating event associations between (1) spinal versus (vs) non-spinal clinical syndrome (2) spinal vs cerebral T2-weighted (T2w) and (3) contrast-enhancing (CE) lesion counts with IgG IF + (vs IgG IF −) or IgM IF + (vs IgM IF −) were investigated by logistic regression adjusted for age and sex, respectively. For serum neurofilament light chain (sNfL) analysis patients were categorized for presence or absence of oligoclonal IgG bands (OCGB), IgG IF and IgM IF (>0% vs 0%, respectively): (1) OCGB −/IgG IF −/IgM IF −; (2) OCGB +/IgG IF −/IgM IF −; (3) OCGB +/IgG IF +/IgM IF −; and (4) OCGB +/IgG IF +/IgM IF +. Associations between categories 2 to 4 vs category 1 with sNfL concentrations were analyzed by robust linear regression, adjusted for sex and MRI parameters. Results: Patients with a spinal syndrome had a 8.36-fold higher odds of IgM IF + (95%CI 3.03–23.03; p < 0.01). Each spinal T2w lesion (odds Ratio 1.39; 1.02–1.90; p = 0.037) and CE lesion (OR 2.73; 1.22–6.09; p = 0.014) was associated with an increased risk of IgM IF + (but not of IgG IF +); this was not the case for cerebral lesions. OCGB +/IgG IF +/IgM IF + category patients showed highest sNfL levels (estimate:1.80; 0.55–3.06; p < 0.01). Interpretation: Intrathecal IgM synthesis is strongly associated with spinal manifestation and independently more pronounced neuroaxonal injury in early MS, suggesting a distinct clinical phenotype and pathophysiology. ANN NEUROL 2022.

Additional file 1. Table S1. Patient and subgroup characteristics.

Background Urinary tract infection (UTI) is diagnosed combining urinary symptoms with demonstration of urine culture growth above a given threshold. Our aim was to compare the diagnostic accuracy of Urine Flow Cytometry (UFC) with urine test strip in predicting bacterial growth and in identifying contaminated urine samples, and to derive an algorithm to identify relevant bacterial growth for clinical use. Methods Species identification and colony-forming unit (CFU/ml) quantification from bacterial cultures were matched to corresponding cellular (leucocytes/epithelial cells) and bacteria counts per μl. Results comprise samples analysed between 2013 and 2015 for which urine culture (reference standard) and UFC and urine test strip data (index tests, Sysmex UX-2000) were available. Results 47,572 urine samples of 26,256 patients were analysed. Bacteria counts used to predict bacterial growth of ≥105 CFU/ml showed an accuracy with an area under the receiver operating characteristic curve of > 93% compared to 82% using leukocyte counts. The relevant bacteriuria rule-out cut-off of 50 bacteria/μl reached a negative predictive value of 98, 91 and 89% and the rule-in cut-off of 250 bacteria/μl identified relevant bacteriuria with an overall positive predictive value of 67, 72 and 73% for microbiologically defined bacteriuria thresholds of 105, 104 or 103 CFU/ml, respectively. Measured epithelial cell counts by UFC could not identify contaminated urine. Conclusions Prediction of a relevant bacterial growth by bacteria counts was most accurate and was a better predictor than leucocyte counts independently of the source of the urine and the medical specialty ordering the test (medical, surgical or others).

Additional file 1.

We aimed to determine in relapsing multiple sclerosis (MS) whether intrathecal synthesis of immunoglobulin (Ig) M and IgG is associated with outcomes reflecting inflammatory activity and chronic worsening. We compared cerebrospinal fluid analysis, clinical and magnetic resonance imaging data, and serum neurofilament light chain (sNfL) levels at baseline and follow-up in 530 patients with relapsing MS. Patients were categorized by the presence of oligoclonal IgG bands (OCGB) and intrathecal synthesis of IgG and IgM (intrathecal fraction [IF]: IgG IF and IgM IF ). Relationships with the time to first relapse, sNfL concentrations, T2-weighted (T2w) lesions, MS Severity Score (MSSS), and time to initiation of high-efficacy therapy were analyzed in covariate-adjusted statistical models. By categorical analysis, in patients with IgM IF the median time to first relapse was 28 months shorter and MSSS on average higher by 1.11 steps compared with patients without intrathecal immunoglobulin synthesis. Moreover, patients with IgM IF had higher sNfL concentrations, more new/enlarging T2w lesions, and higher total T2w lesion counts (all p ≤ 0.01). These associations were absent or equally smaller in patients who were positive for only OCGB or OCGB/IgG IF . Furthermore, quantitative analyses revealed that in patients with IgM IF ≥ median, the time to first relapse and to initiation of high-efficacy therapy was shorter by 32 and by 203 months, respectively (both p < 0.01), in comparison to patients with IgM IF < median. Dose-dependent associations were also found for IgM IF but not for IgG IF with magnetic resonance imaging-defined disease activity and sNfL. This large study supports the value of intrathecal IgM synthesis as an independent biomarker of disease activity and severity in relapsing MS. ANN NEUROL 2021;90:477-489.

International audience; The qualitative evaluation of proteinuria represents a crucial diagnostic step in clinical practice for the classification of renal diseases according to glomerular, tubulo-interstitial, mixed injury or related to monoclonal gammopathy. Combined with the quantitative evaluation, it also allows an assessment of the disease's severity and prognosis as well as the response to treatment. The development of the urine protein profile (UPP) combines specific urine protein assays on a urine spot analyzing glomerular protein markers such as albumin, transferrin and immunoglobulin G, and tubular markers such as alpha-1microglobulin and retinol binding protein, to generate a detailed quantitative and qualitative proteinuria assessment. This short overview proposes to illustrate the diagnostic and prognostic usefulness of UPP in different common clinical situations.

Background/objectives: Neurofilament light chain (NfL) levels in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients correlate with the degree of neuronal injury. To date, little is known about NfL concentrations in the serum of relapsing remitting multiple sclerosis (RRMS) patients and their relationship with CSF levels and magnetic resonance imaging (MRI) measures of disease severity. We aimed to validate the quantification of NfL in serum samples of RRMS, as a biofluid source easily accessible for longitudinal studies. Methods: A total of 31 RRMS patients underwent CSF and serum sampling. After a median time of 3.6 years, 19 of these RRMS patients, 10 newly recruited RRMS patients and 18 healthy controls had a 3T MRI and serum sampling. NfL concentrations were determined by electrochemiluminescence immunoassay. Results: NfL levels in serum were highly correlated to levels in CSF ( r = 0.62, p = 0.0002). Concentrations in serum were higher in patients than in controls at baseline ( p = 0.004) and follow-up ( p = 0.0009) and did not change over time ( p = 0.56). Serum NfL levels correlated with white matter (WM) lesion volume ( r = 0.68, p Conclusion: CSF and serum NfL levels were highly correlated, and serum concentrations were increased in RRMS. Serum NfL levels correlated with MRI markers of WM disease severity. Our findings further support longitudinal studies of serum NfL as a potential biomarker of on-going disease progression and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.

SummaryThis paper presents the case of a 61-year-old female patient who complained about exhaustion and fever during curative therapy, a few weeks after hysterectomie and adnexectomy. Antibiotic therapy could only improve these symptoms though only in the short term. Additionally, a venous port, which had been implanted for the purpose of cytoreduction chemotherapy, was suspected of a catheter infection and was removed. However, this did not lead to a substantial improvement of the patient’s general state of health, but ultimately triggered a sepsis, making necessary treatment in intensive care unit. At this stage, the detailed search for the focus of the infection led to the discovery of an infected thrombosis of the inferior vena cava with bilateral septic pulmonal embolisms and with an abscess. Thus, the source of sepsis had to be removed by surgery, a transfemoral thrombectomy was performed and an inguinal arteriovenous fistula was created. The further course of the disease was without complications; the patient could be released into ambulant treatment 24 days after the surgery. The elective sealing of the arteriovenous fistula was carried out 11 months later. In the follow- up, there were no hints for infection; the deep venous system in particular did not indicate any new thrombosis or of residual thrombi, with the tumor follow-up-care showing a complete remission.

Objective: We investigated the correlation of anti-myelin oligodendrocyte glycoprotein- (anti-MOG) and anti-myelin basic protein antibodies (anti-MBP) in serum of CIS patients with inflammatory signs in MRI and in CSF and, as previously suggested, the incidence of more frequent and rapid progression to clinically definite MS (CDMS). Methods: 133 CIS patients were analysed for anti-MOG and anti-MBP (Western blot). Routine CSF and cranial MRI (quantitatively and qualitatively) measures were analyzed. 55 patients had a follow-up of at least 12 months or until conversion to CDMS. Results: Patients with anti-MOG and anti-MBP had an increased intrathecal IgG production and CSF white blood cell count (p = 0.048 and p = 0.036). When anti-MBP alone, or both antibodies were present the cranial MRI showed significantly more T2 lesions (p = 0.007 and p = 0.01, respectively). There was a trend for more lesion dissemination in anti-MBP positive patients (p = 0.076). Conversely, anti-MOG- and/or anti-MBP failed to predict conversion to CDMS in our follow-up group (n = 55). Only in female patients with at least one MRI lesion (n = 34) did the presence of anti-MOG correlate with more frequent (p = 0.028) and more rapid (p = 0.0209) transition to CDMS. Conclusions: Presence of anti-MOG or anti-MBP or both was not significantly associated with conversion to CDMS in our CIS cohort. However, patients with anti-MOG and anti-MBP had higher lesion load and more disseminated lesions in cranial MRI as well as higher values for CSF leucocytes and intrathecal IgG production. Our data support a correlation of anti-MOG and anti-MBP to inflammatory signs in MRI and CSF. The prognostic value of these antibodies for CDMS, however, seems to be less pronounced than previously reported

Background Several cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. However, predictors might be more or less powerful depending on the characteristics of the MCI sample. Objective To investigate which cognitive markers and biomarkers predict conversion to AD dementia and course of cognitive functioning in a MCI sample with a high proportion of early-stage MCI patients. Methods Variables known to predict progression in MCI patients and hypothesized to predict progression in early-stage MCI patients were selected. Cognitive (long-delay free recall, regional primacy score), imaging (hippocampal and entorhinal cortex volumes, fornix fractional anisotropy), and CSF (Aβ1-42/t-tau, Aβ1-42) variables from 36 MCI patients were analyzed with Cox regression and mixed-effect models to determine their individual and combined abilities to predict time to conversion to AD dementia and course of global cognitive functioning, respectively. Results Those variables hypothesized to predict the course of early-stage MCI patients were most predictive for MCI progression. Specifically, regional primacy score (a measure of word-list position learning) most consistently predicted conversion to AD dementia and course of cognitive functioning. Both the prediction of conversion and course of cognitive functioning were maximized by including CSF Aβ1-42 and fornix integrity biomarkers, respectively, indicating the complementary information carried by cognitive variables and biomarkers. Conclusion Predictors of MCI progression need to be interpreted in light of the characteristics of the respective MCI sample. Future studies should aim to compare predictive strengths of markers between early-stage and late-stage MCI patients.

Background: Serum neurofilament light chain (sNfL) levels represent a promising marker of neuroaxonal injury. They are elevated in several neurological conditions, but their importance in cerebrovascular diseases remains unclear. In a proof of concept study, we compared sNfL levels with clinical characteristics and outcome in patients with cervical artery dissection (CeAD). Methods: A total of 49 non-traumatic CeAD patients were included. sNfL levels were measured by high-sensitivity electrochemiluminescence immunoassay. Levels were compared with regard to (i) type of presenting symptoms (local symptoms only (n = 8), transient ischemic attack (TIA; n = 10) or ischemic stroke (n = 31)), (ii) stroke severity quantified by National Institute of Health Stroke Scale (NIHSS), (iii) time interval between onset of symptoms and blood sampling and (iv) 3-month outcome as measured by the modified Rankin Scale score. Analyses were performed using univariate and multivariate linear and ordinal regression models. Results: CeAD patients presenting with stroke had significantly higher sNfL levels (median 108.9 pg/ml, interquartile range (37.8-427.7)) than patients with TIA (16.4 pg/ml (8.7-36.3), p = 0.002) or local symptoms (23.4 pg/ml (17.8-30.8), p = 0.0007). Among stroke patients, sNfL levels were positively associated with both NIHSS (p = 0.0002) and time between stroke onset and serum sampling (p = 1.9 × 10-6). Higher sNfL levels were associated with unfavorable outcome at 3 months (OR 4.67, 95% CI 1.69-12.95, p = 0.003). However, this association lost significance after adjustment for NIHSS. The highest sNfL level was observed in a TIA patient who had ischemic stroke 1 day after serum sampling for sNfL measurement. Conclusion: sNfL levels were increased in CeAD patients presenting with stroke, correlated with clinical severity and were influenced by the time point of blood sampling. The prognostic meaning of sNfL in CeAD deserves further testing.

SummaryA case of bilateral iliofemoral thrombosis in a 17-year-old [male] patient is presented. It was only revealed during bilateral transfemoral thrombectomy that the thrombosis was due to previous inferior vena cava occlusion. This required a complex interventional reconstruction of the vena cava with secondary stenting of both renal veins. The postoperative venogram showed blood outflow from the left renal vein into the portal vein and from the right renal vein into the inferior vena cava via collaterals. At follow-up presentation, the patient was asymptomatic with normal findings on computed tomography scanning.

SummaryThe case reported here involves a 72-year-old female patient with right-sided popliteal vein aneurysm, which became apparent during follow-up ultrasound scanning after deep venous thrombosis of the left leg with pulmonary embolism. Due to the size of the aneurysm, the decision was made to perform surgery. The aneurysm was tangentially resected by means of plication. Aneurysms of the deep venous system carry a considerable risk of a thromboembolic event and therefore require treatment, even when they are asymptomatic. Surgical treatment of an aneurysm of the deep leg veins is a safe and low-risk procedure for the prevention of pulmonary embolism.

Subarachnoid haemorrhage (SAH) has a high mortality and morbidity rate. Early SAH diagnosis allows the early treatment of a ruptured cerebral aneurysm, which improves the prognosis. Diagnostic cerebrospinal fluid (CSF) analyses may be performed after a negative computed tomography scan, but the precise analytical methods to be used have been debated. Here, we summarize the scientific evidence for different CSF methods for SAH diagnosis and describe their implementation in different countries. The principle literature search was conducted using PubMed and Scopus with the search items “cerebrospinal fluid”, “subarachnoid haemorrhage”, and “diagnosis”. CSF analyses for SAH include visual examination, red blood cell counts, spectrophotometry for oxyhaemoglobin or bilirubin determination, CSF cytology, and ferritin measurement. The methods vary in availability and performance. There is a consensus that spectrophotometry has the highest diagnostic performance, but both oxyhaemoglobin and bilirubin determinations are susceptible to important confounding factors. Visual inspection of CSF for xanthochromia is still frequently used for diagnosis of SAH, but it is advised against because spectrophotometry has a superior diagnostic accuracy. A positive finding of CSF bilirubin is a strong indicator of an intracranial bleeding, whereas a positive finding of CSF oxyhaemoglobin may indicate an intracranial bleeding or a traumatic tap. Where spectrophotometry is not available, the combination of CSF cytology for erythrophages or siderophages and ferritin is a promising alternative.

Zusammenfassung Die Analyse von spezifischen Proteinen im zweiten Morgenurin, bezogen auf den Kreatiningehalt der Probe, erlaubt heute nicht nur den Nachweis oder den Ausschluss von Nierenerkrankungen, sondern darüber hinaus auch die Differenzierung und Verlaufskontrolle von Nephropathien. Störungen lassen sich aufgrund ihres Markerproteinprofils in solche mit hauptsächlich glomerulärem oder tubulärem Anteil und zusätzlich in weitere Untergruppen einteilen. Im Zusammenhang mit den Teststreifenresultaten kann die Quelle einer Blutung mit spezifischen Quotienten näher eingegrenzt und Kontaminationen können von tatsächlichen renalen Proteinurien unterschieden werden. Eine Plausibilitätsprüfung und Interpretation der erhaltenen Ergebnisse ist unbedingt erforderlich. Da eineVielzahl von Regeln überprüft werden muss, ist eine Berechnung und Darstellung der Ergebnisse nur mit Hilfe von wissensbasierten Systemen in Kombination mit einer grafischen Befunddarstellung sinnvoll.

The increased analytical sensitivity of capillary electrophoresis detects additional irregularities that are suspicious for a monoclonal component. This is most noticeable in the beta-1-, beta-2- and gamma-globulin fractions. The causes of non-monoclonal irregularities are manifold, but are rarely reported back to the ordering physician. This article reviews the basic concepts to correctly identify irregularities, monoclonal and oligoclonal peaks by capillary electrophoresis. It then focuses on detecting and reporting typical non-monoclonal irregularities according to their electrophoresis fractions as well as their possible clinical implications.

Background. Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes and tubular epithelial cells. We have previously shown that α-Gal A is delivered to these cells by different pathways involving different receptors. This study investigated the long-term changes in albuminuria, estimated glomerular filtration rate (eGFR) and urinary markers of both glomerular and tubular dysfunction in women with Fabry disease treated with ERT. Methods. A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile, including the glomerular marker IgG, the tubular markers α1-microglobulin and retinol-binding protein (RBP), and the shared tubular and glomerular markers albumin and transferrin. Results. ERT was associated with a significant reduction in albuminuria and a relatively stable eGFR. The decrease in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. Conclusions. The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestations.