Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers, predicting disease subtype and progression to improve individually tailored treatment. Using the two-dimensional difference gel electrophoresis (2-D-DIGE) technology for comparative analysis, we compared CSF samples from patients with MS of the relapse-remitting type (RRMS, n = 12) and from patients with clinically isolated syndrome (CIS, n = 12) suggestive of a first demyelinating attack with neurologically normal controls. Protein spots that showed more than two-fold difference between patients and controls were selected for further analysis with MALDI-TOF mass spectrometry. Immunoblot analysis was performed to confirm the validity of individual candidate proteins. In RRMS, we identified 1 up-regulated and 10 down-regulated proteins. In CIS, 2 up-regulated and 11 down-regulated proteins were identified. One of these proteins (Apolipoprotein A1) was confirmed by immunoblot. Though the pathophysiological role of these proteins still remains to be elucidated in detail and further validation is needed, these findings may have a relevant impact on the identification of disease-specific markers.

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Background Cardiac amyloidosis (CA) is an infiltrative disease characterised by accumulation of amyloid deposits in the extracellular space of the myocardium—comprising transthyretin (ATTR) and light chain (AL) amyloidosis as the most frequent subtypes. Histopathological proof of amyloid deposits by endomyocardial biopsy (EMB) is the gold standard for diagnosis of CA. Cardiovascular magnetic resonance (CMR) allows non-invasive workup of suspected CA. We conducted a multi-centre study to assess the diagnostic value of CMR in comparison to EMB for the diagnosis of CA. Methods We studied N = 160 patients characterised by symptoms of heart failure and presence of left ventricular (LV) hypertrophy of unknown origin who presented to specialised cardiomyopathy centres in Germany and underwent further diagnostic workup by both CMR and EMB. If CA was diagnosed, additional subtyping based on EMB specimens and monoclonal protein studies in serum was performed. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as native and post-contrast T1-mapping (in a subgroup)—allowing to measure extracellular volume fraction (ECV) of the myocardium. Results An EMB-based diagnosis of CA was made in N = 120 patients (CA group) whereas N = 40 patients demonstrated other diagnoses (CONTROL group). In the CA group, N = 114 (95%) patients showed a characteristic pattern of LGE indicative of CA. In the CONTROL group, only 1/40 (2%) patient showed a “false-positive” LGE pattern suggestive of CA. In the CA group, there was no patient with elevated T1-/ECV-values without a characteristic pattern of LGE indicative of CA. LGE-CMR showed a sensitivity of 95% and a specificity of 98% for the diagnosis of CA. The combination of a characteristic LGE pattern indicating CA with unremarkable monoclonal protein studies resulted in the diagnosis of ATTR-CA (confirmed by EMB) with a specificity of 98% [95%-confidence interval (CI) 92–100%] and a positive predictive value (PPV) of 99% (95%-CI 92–100%), respectively. The EMB-associated risk of complications was 3.13% in this study—without any detrimental or persistent complications. Conclusion Non-invasive CMR shows an excellent diagnostic accuracy and yield regarding CA. When combined with monoclonal protein studies, CMR can differentiate ATTR from AL with high accuracy and predictive value. However, invasive EMB remains a safe invasive gold-standard and allows to differentiate CA from other cardiomyopathies that can also cause LV hypertrophy.

Background: Adenosine is used in stress perfusion cardiac imaging to reveal myocardial ischemia by its vasodilator effects. Caffeine is a competitive antagonist of adenosine. However, previous studies reported inconsistent results about the influence of caffeine on adenosine's vasodilator effect. This study assessed the impact of caffeine on the myocardial perfusion reserve index (MPRI) using adenosine stress cardiovascular magnetic resonance imaging (CMR). Moreover, we sought to evaluate if the splenic switch-off sign might be indicative of prior caffeine consumption. Methods: Semiquantitative perfusion analysis was performed in 25 patients who underwent: 1) caffeine-naïve adenosine stress CMR demonstrating myocardial ischemia and, 2) repeat adenosine stress CMR after intake of caffeine. MPRI (global; remote and ischemic segments), and splenic perfusion ratio (SPR) were assessed and compared between both exams. Results: Global MPRI after caffeine was lower vs. caffeine-naïve conditions (1.09 ± 0.19 vs. 1.24 ± 0.19; p < 0.01). MPRI in remote myocardium decreased by caffeine (1.24 ± 0.19 vs. 1.49 ± 0.19; p < 0.001) whereas MPRI in ischemic segments (0.89 ± 0.18 vs. 0.95 ± 0.23; p = 0.23) was similar, resulting in a lower MPRI ratio (=remote/ischemic segments) after caffeine consumption vs. caffeine-naïve conditions (1.41 ± 0.19 vs. 1.64 ± 0.35, p = 0.01). The SPR was unaffected by caffeine (SPR 0.38 ± 0.19 vs. 0.38 ± 0.18; p = 0.92). Conclusion: Caffeine consumption prior to adenosine stress CMR results in a lower global MPRI, which is driven by the decreased MPRI in remote myocardium and underlines the need of abstinence from caffeine. The splenic switch-off sign is not affected by prior caffeine intake.