Immune phenotyping study revealing caveats regarding a switch from fingolimod to cladribine.

BACKGROUND: Recent data support a key role of B cells in the pathogenesis of multiple sclerosis. Due to the pronounced effect of cladribine on memory B cells, we initiated an immune phenotyping study, which included monitoring of memory B cells of patients newly assigned to this treatment option. A patient with ongoing disease activity in the first year of cladribine after a long-standing fingolimod treatment caught our attention. OBJECTIVE: To report about differences in the immune phenotype of the case compared to patients without disease activity and to discuss possible causes for the deviations as caveats regarding treatment sequelae. METHODS: Clinical data and immune phenotyping data collected at baseline (before treatment) and after three, six and ten/twelve months after cladribine initiation were compared between our case and six patients with a stable disease course (controls). RESULTS: Both, the case and controls showed similar reductions of memory B cells in response to cladribine. The case however, showed an accelerated repopulation dynamic of naïve B cells with an almost 3-fold hyperrepopulation compared to baseline levels, and lower pre-treatment levels of CD4+ and CD8+ T cells and memory B cells compared to controls. CONCLUSION: We propose a prolonged pre-treatment with fingolimod as possible cause for the lack of response to cladribine. Autoreactive cells sequestrated within lymph nodes may have evaded cladribine depletion on top of a delay of recirculating regulatory T cells. In addition, we want to raise awareness of the importance of monitoring T and B cells for bridging the current lack of evidence regarding sequencing therapies in the real life setting.

Serum IgG levels and mortality in patients with severe sepsis and septic shock : The SBITS data.

BACKGROUND: The role of intravenous immune globulin (Ig) therapy in patients with severe sepsis and septic shock is discussed controversially. Low initial IgG levels could help to identify those patients who might benefit from an adjunctive Ig treatment. OBJECTIVES: To investigate the effect of initial serum IgG levels on 28-day mortality in patients with severe sepsis and septic shock. MATERIALS AND METHODS: In this retrospective analysis of the SBITS trial data, 543 patients were allocated to four groups (quartiles) depending on their initial serum IgG levels (1: IgG ≤ 6.1 g/l; 2: IgG 6.2-8.4 g/l; 3: IgG 8.5-11.9 g/l; 4: IgG > 11.9 g/l). The third quartile was taken as the reference quartile. For the applied logistic regression model clinically relevant confounders were defined and integrated into further risk-adjusted calculations. RESULTS: Patients with the lowest IgG levels had a mortality rate similar to those patients with initial IgG levels in the second and third quartile, representing the physiological IgG range in healthy people. Surprisingly, patients with the highest IgG levels even showed a significantly higher mortality in a risk-adjusted calculation compared to the reference quartile (OR 1.69, CI 1.01-2.81, p = 0.05). Subgroup analyses revealed that initial IgG levels were of no prognostic value in patients presenting with vasopressor-dependent septic shock on admission as well as in patients with either gram-positive or gram-negative sepsis. CONCLUSIONS: Initially low IgG levels do not discriminate between survival and nonsurvival in patients with severe sepsis and septic shock. Therefore, low IgG cannot help to identify those patients who might benefit from an adjunctive IgG sepsis therapy. Whether a high initial IgG serum level is an independent mortality risk factor needs to be investigated prospectively.

2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry.

OBJECTIVES: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. BACKGROUND: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. METHODS: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. RESULTS: During the current observation 37,788 doses of Gadolinium based contrast agent were administered to 37,788 patients. The mean dose was 24.7 ml (range 5-80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12%). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05% (linear non-ionic agent gadodiamide) to 0.42% (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05% (risk stratification in suspected CAD) to 0.22% (viability in known CAD). CONCLUSIONS: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the "off-label" use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events.

Predicting outcome of status epilepticus.

BACKGROUND: Status epilepticus (SE) is a frequent neurological emergency complicated by high mortality and often poor functional outcome in survivors. The aim of this study was to review available clinical scores to predict outcome. METHODS: Literature review. PubMed Search terms were "score", "outcome", and "status epilepticus" (April 9th 2015). Publications with abstracts available in English, no other language restrictions, or any restrictions concerning investigated patients were included. RESULTS: Two scores were identified: "Status Epilepticus Severity Score--STESS" and "Epidemiology based Mortality score in SE--EMSE". A comprehensive comparison of test parameters concerning performance, options, and limitations was performed. Epidemiology based Mortality score in SE allows detailed individualization of risk factors and is significantly superior to STESS in a retrospective explorative study. In particular, EMSE is very good at detection of good and bad outcome, whereas STESS detecting bad outcome is limited by a ceiling effect and uncertainty of correct cutoff value. Epidemiology based Mortality score in SE can be adapted to different regions in the world and to advances in medicine, as new data emerge. In addition, we designed a reporting standard for status epilepticus to enhance acquisition and communication of outcome relevant data. A data acquisition sheet used from patient admission in emergency room, from the EEG lab to intensive care unit, is provided for optimized data collection. CONCLUSION: Status Epilepticus Severity Score is easy to perform and predicts bad outcome, but has a low predictive value for good outcomes. Epidemiology based Mortality score in SE is superior to STESS in predicting good or bad outcome but needs marginally more time to perform. Epidemiology based Mortality score in SE may prove very useful for risk stratification in interventional studies and is recommended for individual outcome prediction. Prospective validation in different cohorts is needed for EMSE, whereas STESS needs further validation in cohorts with a wider range of etiologies. This article is part of a Special Issue entitled "Status Epilepticus".

Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit.

INTRODUCTION: In refractory status epilepticus (SE), because of subcellular maladaptive changes, GABAergic drugs are no longer effective, and the excitatory neurotransmitter glutamate (Glu) plays a major role in seizure perpetuation. Perampanel (PER, licensed since 09/2012) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. METHODS: We analyzed treatment response, seizure outcome, and adverse effects of add-on treatment with perampanel in patients with refractory status epilepticus in the Neurological Intensive Care Unit (NICU), Salzburg, Austria between 09/2012 and 11/2014 by retrospective chart review. RESULTS: Twelve patients (75% women) with refractory status epilepticus were treated with PER administered per nasogastric tube between 09/2012 and 11/2014. Median age was 75 years [range: 60-91]. The most frequent SE type was nonconvulsive SE (NCSE) with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose de novo, with an acute symptomatic cause in five patients (42%). Cerebrovascular diseases (4/12, 33%) and cerebral tumors (4/12, 33%) were the most common etiologies. Perampanel was given after a median number of four antiepileptic drugs [range: 2-7] and a median time of 1.5 days [range: 0.8-18.3]. In one patient (8%), clinical improvement was observed within 24h and EEG improvement within 60 h after administration of PER, while in another patient (8%), clinical and EEG improvement was observed more than 48 h after administration. Median initial dose was 4 mg [range: 2-12; SD: 4.11], titrated up to a median of 12 mg [range: 4-12] in steps of 2 to 4 mg per day. No adverse effects were reported regarding cardiorespiratory changes or laboratory parameters. Outcomes after SE were moderate disability in five patients (42%), death in three patients (25%), and persistent vegetative state in two patients (17%). CONCLUSION: Though glutamate plays a major role in seizure perpetuation, the noncompetitive AMPA receptor antagonist PER could only ameliorate seizure activity in a few patients with refractory SE. The long duration of SE before the administration of PER via nasogastric tube, as well as relatively low doses of PER, might be responsible for the modest result. Perampanel was well tolerated, and no adverse events were reported. This article is part of a Special Issue entitled Status Epilepticus.

High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis.

Strongly decreased leucocyte counts and a reduced CD4/CD8 T cell ratio in the cerebrospinal fluid (CSF) of natalizumab (NZB)-treated multiple sclerosis (MS) patients may have implications on central nervous (CNS) immune surveillance. With regard to NZB-associated progressive multi-focal leucoencephalopathy, we aimed at delineating a relationship between free NZB, cell-bound NZB, adhesion molecule (AM) expression and the treatment-associated shift in the CSF T cell ratio. Peripheral blood (PB) and CSF T cells from 15 NZB-treated MS patients, and CSF T cells from 10 patients with non-inflammatory neurological diseases and five newly diagnosed MS patients were studied. Intercellular adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), NZB saturation levels, and T cell ratios were analysed by flow cytometry. NZB concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Lower NZB saturation levels (P<0.02) and a higher surface expression of ICAM-1 and LFA-1 (P<0.001) were observed on CSF CD8 T cells. CSF T cell ratios (0.3-2.1) and NZB concentrations (0.01-0.42 µg/ml) showed a pronounced interindividual variance. A correlation between free NZB, cell-bound NZB or AM expression levels and the CSF T cell ratio was not found. Extremely low NZB concentrations and a normalized CSF T cell ratio were observed in one case. The differential NZB saturation and AM expression of CSF CD8 T cells may contribute to their relative enrichment in the CSF. The reduced CSF T cell ratio appeared sensitive to steady-state NZB levels, as normalization occurred quickly. The latter may be important concerning a fast reconstitution of CNS immune surveillance.

Natalizumab saturation: biomarker for individual treatment holiday after natalizumab withdrawal?

BACKGROUND: More and more patients with multiple sclerosis (MS) switch from natalizumab to fingolimod because of the risk of progressive multifocal leukoencephalopathy. The duration of the treatment holiday is still under debate referring to a possible recurrence of disease activity. AIM OF THE STUDY: The aim of this study was to evaluate the prognostic value of natalizumab saturation on T cells for the recurrence of clinical and radiological disease activity. METHODS: Cell surface-bound natalizumab saturation (in%) of CD8+ and CD4+ T cells from five patients with MS was determined before initiation of fingolimod by flow cytometry and related to clinical and MRI outcome during a 6-month follow-up. RESULTS: In two patients with either clinical or radiological disease activity, the natalizumab saturation on CD8+ and CD4+ T cells was <30%. In contrast, the remaining three patients with absence of disease activity had a median natalizumab saturation of 70% (range 59-79%) on CD4+ and 66% (range 52-68%) on CD8+ T cells. CONCLUSIONS: The data of this pilot study indicate that clinical and radiological disease activity is closely linked to natalizumab saturation at the time point of switch. The determination of natalizumab saturation may be an essential tool to monitor cessation of natalizumab treatment.

Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis.

An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3(+) CD8(+) , CD3(+) CD4(+) ), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3(+) CD4(+) T cells, B cells), VLA-4 (CD3(+) CD8(+) T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3(+) CD4(+) ) and VLA-4 (CD3(+) CD4(+) , CD3(+) CD8(+) , NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.

Circadian rhythmicity of inflammatory serum parameters: a neglected issue in the search of biomarkers in multiple sclerosis.

Inflammatory serum parameters are intensely investigated in the search of biomarkers for disease activity and treatment response in multiple sclerosis (MS). A reason for contradictory results might be the timing of blood collection for analyzing serum concentrations of inflammatory parameters which are subject to diurnal changes. We included 34 untreated patients with relapsing-remitting MS and 34 age- and sex-matched healthy controls. 12 MS patients showed acute disease activity in corresponding MRI scans. Blood samples were obtained at 7.00, 11.00 am, 2.30, 6.00 and 9.30 pm within 1 day. We determined serum levels of cortisol and inflammatory markers including soluble tumor necrosis factor-beta (sTNF-ß), soluble TNF-Receptor-1 (sTNF-R1) and -2 (sTNF-2), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) by ELISA. We observed significantly higher serum levels of sTNF-R1 (p < 0.001) and sTNF-R2 (p < 0.001) in the morning and a significant decline of sICAM-1 (p < 0.005) and sVCAM-1 (p < 0.001) in the afternoon in both, MS patients and healthy controls. Comparison of diurnal serum levels between MS patients with active versus with non-active disease revealed significantly higher serum levels of sVCAM-1 (p < 0.05) around noon and in the early afternoon in MS patients with active disease. A significant decline of sICAM-1 (p < 0.05) in the afternoon was seen in MS patients with active and non-active disease. Our data indicate that increased awareness of potential diurnal serum concentration changes of biomarkers can eliminate one major cause of biased data as they occur in most of the investigated immunological parameters.

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy.

Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients.

Tricuspid annular plane systolic excursion assessed using MRI for semi-quantification of right ventricular ejection fraction.

OBJECTIVE: Accurate determination of right ventricular volume and ejection fraction (RVEF) is established using MRI. Automatic contour detection of the right ventricular endocardial border is not established in clinical practice, resulting in considerable manual efforts to quantify RVEF. Using transthoracic echocardiography (TTE), the tricuspid annular plane systolic excursion (TAPSE) has proved its worth for quantification of RVEF and risk prediction. Therefore, the aim of this study was to clarify whether TAPSE assessed with MRI as a fast and easily obtainable parameter correlated with volumetric quantification of RVEF. METHODS: Right ventricular volumes and RVEF were measured with the standardised slice-summation method at MRI. MRI-TAPSE was defined as maximum apical excursion of lateral tricuspid annular plane and measured in a four-chamber view using steady-state free precession sequences. Additionally, MRI-TAPSE was compared with TAPSE assessed using TTE. RESULTS: 76 consecutive patients (aged 58±17 years) were examined. At MRI, right end-diastolic volumes were 97±36 ml, right end-systolic volumes were 57±27 ml and the mean RVEF was 42±14%. MRI-TAPSE was determined with 19±6 mm and correlated well at linear regression analysis with volumetric RVEF (r=0.72, p<0.001). Furthermore, MRI-TAPSE discriminated sufficiently between patients with impaired and normal RVEF. Multiplying MRI-TAPSE by 2.5 led to values close to the RVEF by volumetry. Additionally, MRI-TAPSE correlated well with TAPSE determined using TTE. The inter- and intra-observer variabilities of MRI-TAPSE determination were low (3.1% and 1.8%). CONCLUSION: TAPSE assessed with MRI is a fast and easily obtainable parameter which correlates well with volumetric quantification of RVEF.

Isolated leptomeningeal infiltration of a primary CNS B-cell lymphoma diagnosed by flow cytometry and confirmed by necropsy.

BACKGROUND: The diagnosis of the isolated leptomeningeal involvement of a primary central nervous system B-cell lymphoma without parenchyma lesions may be difficult. Patients with leptomeningeal meningeosis lymphomatosa can present with various neurologic deficits. AIMS OF THE STUDY: To demonstrate the impact of cerebrospinal fluid (CSF) flow cytometry in the diagnosis of an isolated leptomeningeal manifestation of B-cell lymphoma by presenting an interesting case report. METHODS: Flow cytometric analysis of B-cell monoclonality of the CSF was performed as complementary diagnostic procedure in addition to CSF cytology. Final diagnosis was confirmed by necropsy. RESULTS: We suspected isolated leptomeningeal manifestation of B-cell lymphoma with palsy of the VI and VII cranial nerves in a 79-year-old male, because of mononuclear pleocytosis in CSF. Interestingly, the decisive diagnostic hint was given by implementation of flow cytometry of the CSF. Diagnosis was confirmed by postmortem autopsy. CONCLUSION: Our case shows that flow cytometry of the CSF in addition to conventional CSF cytology has the potential to accelerate diagnosis of lymphomeningeal infiltration of B-cell lymphoma.

Molecular evidence of transient therapeutic effectiveness of natalizumab despite high-titre neutralizing antibodies.

Natalizumab is a humanized monoclonal antibody directed against the alpha-4 integrin subunit of very late activation antigen-4 (VLA-4). Natalizumab neutralizing antibodies (NAB) have been found to significantly reduce beneficial effects of natalizumab treatment in multiple sclerosis. We investigated interactions of NAB with natalizumab by serial measurements of alpha-4 integrin levels on peripheral blood mononuclear cells using flow cytometry. In addition, serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), the endothelial ligand of VLA-4, and serum NAB were serially determined. Natalizumab infusion led to a transient reduction in alpha-4 integrin levels on immune cells and serum sVCAM-1 levels along with serum negativity of NAB lasting for a few days post-infusion. Apparently, the high-dose effect of freshly infused natalizumab resulted in a transient neutralization of NAB possibly involving a transient therapeutic effectiveness.

Adhesion molecules are promising candidates to establish surrogate markers for natalizumab treatment.

BACKGROUND: Natalizumab is the first monoclonal antibody therapy approved for multiple sclerosis (MS). Its therapeutic mechanism is the blockade of the α4-integrin subunit of the adhesion molecule (AM) very late activation antigen-4 (VLA-4), which leads to an inhibition of immune cell extravasation into the central nervous system (CNS). METHODS: We investigated changes in the expression levels of unblocked α4-integrin and further AM (intercellular adhesion molecule-1, -2, -3 (cICAM-1, -2, -3), leukocyte function associated antigen-1 (LFA-1)) on peripheral blood mononuclear cells (PBMC) determined by flow cytometry from 25 patients with MS before the first natalizumab infusion and before the fourth infusion. In 15 MS patients AM expression was evaluated every 3 months over 1 year. RESULTS: We found a significant decrease (p < 0.0001) of unblocked α4-integrin cell surface expression on all investigated PBMC subsets (T cells -61.7%, B cells -69.1%, monocytes/macrophages -46.4%) in the blood of MS patients after 3 months of natalizumab treatment. Moreover, a continuous decrease (p < 0.05) of unblocked α4-integrin expression levels was seen after 3, 6, 9, and 12 months. As a secondary effect, expression levels of the other investigated AM were differentially affected. CONCLUSIONS: Results show a sustained decrease of unblocked α4-integrin expression not only in all patients but also in all investigated PBMC subsets. This probably results in a continuously decreasing transmigration of PBMC into the CNS and may explain the improved clinical efficacy in the second treatment year and also the increasing risk of progressive multifocal leukoencephalopathy during long-term natalizumab therapy. We conclude that AM expression profiles are promising candidates for the development of a biomarker system to determine both natalizumab treatment response and patients at risk for opportunistic CNS infections.

Relationship between thrombin generation and carotid intima-media thickness.

UNLABELLED: Increasing evidence indicates that thrombin plays a role not only in thrombosis but also in the progression of atherosclerosis. AIM: The relationship between thrombin generation and intima-media thickness (IMT) as an index of subclinical atherosclerosis was investigated. Participants, material, methods: We examined 163 asymptomatic middle-aged persons free of overt clinical atherosclerotic disease. They underwent ultrasonography of the common carotid arteries. In addition, thrombin generation was measured by means of CAT (calibrated automated thrombography). For our study we divided the healthy study participants into three age groups (<45, 45-60 and >60 years). RESULTS: A significant positive correlation was seen between endogenous thrombin potential (ETP) (p = 0.012), time to peak (TTP) (p = 0.033) start tail (p = 0.007) and carotid IMT in the group of healthy volunteers younger than 45 years. CONCLUSION: We demonstrated that in adults younger than 45 years without clinically overt atherosclerotic disease ETP was significantly associated with carotid IMT. It is tempting to speculate that ETP may serve as an index for subclinical atherosclerosis in persons below 45 years.

Clinical applications of cardiac magnetic resonance imaging.

As a direct result of the rapid technical progress which has been realized regarding hardware and software, cardiovascular magnetic resonance imaging (CMR) is increasingly established as an important method in the diagnosis of cardiovascular disease. Numerous clinical and experimental studies have demonstrated the equality or even superiority of CMR compared to other imaging modalities such as nuclear medicine or transthoracic echocardiography. Particular strengths of CMR are the ability to overcome anatomical limitations (such as poor acoustic window), a multimodality approach to comprehensively answer various aspects of cardiac disease, and the absence of ionizing radiation during the exam. Main clinical applications of CMR include assessment of ventricular function, myocardial viability, myocardial perfusion, valvular disease, differential diagnosis of inflammatory heart disease and cardiomyopathies, congenital heart disease and structural abnormalities. In the assessment of coronary artery disease (CAD) by CMR, analysis of global and regional myocardial function is enhanced by examination of myocardial viability and perfusion. This non-invasive diagnostic ''triad'' confers CMR a unique methodological strength for a comprehensive evaluation of CAD within one single exam session. In particular, late gadolinium enhancement scar imaging by CMR is currently the most accurate non-invasive method to examine myocardial viability. In several studies on the prognostic value of CMR in CAD assessment, normal adenosine-stress CMR was highly predictive for a good prognosis, thus able to identify patients in whom invasive coronary angiography can be deferred safely. Regarding myocarditis, CMR is evolving as the most accurate imaging technique. Challenges for future development of the role of CMR in clinical routine will most likely not only include technical improvement, but also a larger CMR scanner availability, optimized cost-efficiency, increased awareness and competence to be achieved by an extended education and training in CMR.

[Prolonged migrainous aura and acute ischemic insult. Differential diagnosis by diffusion- and perfusion-weighted cMRI]. / Prolongierte Migräneaura vs. akuter ischämischer Insult. Sichere Diagnose mittels cMRT im "Lyse-Fenster"?

BACKGROUND: According to the "time is brain" concept, differential diagnosis of acute stroke and prolonged migrainous aura is of vital importance in this era of systemic thrombolysis for acute cerebral ischemia. We demonstrate the value of cerebral magnetic resonance imaging (cMRI) in acute situations by presenting two patients. PATIENTS AND METHODS: Two patients were sent to our hospital for lysis treatment after the sudden appearance of global aphasia and slight right-sided hemiparesis. Further exploration was impossible due to the aphasia, and therefore we performed diffusion- and perfusion-weighted cMRI. RESULTS: We excluded acute cerebral infarction by the aid of diffusion-weighted cMRI, however left-sided cerebral hypoperfusion was seen in both patients. After resolution of neurologic symptoms, unilateral headache occurred and both patients reported pre-existing migraine with aura. CONCLUSION: Hypoperfusion of the malfunctioning brain region contralateral to the affected side of the body has been described on cMRI in only a few patients with prolonged migrainous aura. We conclude from our two cases that--provided rapid availability--cMRI can add important information for differential diagnosis, in particular when lysis therapy is a treatment option.