Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study.

BACKGROUND: Hemolytic uremic syndrome related to Shiga-toxin-secreting Escherichia coli infection (STEC-HUS) remains a common cause of acute kidney injury in young children. No specific treatment has been validated for this severe disease. Recently, experimental studies highlight the potential role of complement in STEC-HUS pathophysiology. Eculizumab (EC), a monoclonal antibody against terminal complement complex, has been used in severe STEC-HUS patients, mostly during the 2011 German outbreak, with conflicting results. METHODS: On behalf of the French Society of Pediatric Nephrology, we retrospectively studied 33 children from 15 centers treated with EC for severe STEC-HUS. Indication for EC was neurologic involvement in 20 patients, cardiac and neurologic involvement in 8, cardiac involvement in 2, and digestive involvement in 3. Based on medical status at last follow-up, patients were divided into two groups: favorable (n = 15) and unfavorable outcomes (n = 18). RESULTS: Among patients with favorable outcome, 11/14 patients (79%) displayed persistent blockade of complement activity before each EC reinjection. Conversely, in patients with unfavorable outcome, only 9/15 (53%) had persistent blockade (p = n.s.). Among 28 patients presenting neurological symptoms, 19 had favorable neurological outcome including 17 with prompt recovery following first EC injection. Only two adverse effects potentially related to EC treatment were reported. CONCLUSIONS: Taken together, these results may support EC use in severe STEC-HUS patients, especially those presenting severe neurological symptoms. The study, however, is limited by absence of a control group and use of multiple therapeutic interventions in treatment groups. Thus, prospective, controlled trials should be undertaken.

What is the Relevance of the Systematic Use of Gadolinium During the MRI Follow-Up of Multiple Sclerosis Patients Under Natalizumab?

BACKGROUND: Multiple sclerosis (MS) patients represent a population potentially affected by the intracerebral accumulation of gadolinium-based contrast agents (GBCA) due to repeated magnetic resonance imaging (MRI) performed during their lifetime; however, MRI is still the best tool to monitor MS inflammatory activity. OBJECTIVE: This study aimed to evaluate the relevance of GBCA injections during the MRI follow-up of MS patients under natalizumab (Tysabri) treatment. METHODS: The MRI data results were retrospectively reviewed in a monocentric study (University Hospital of Toulouse, France) from all consecutive patients treated with natalizumab from January 2014 to January 2017. For each examination during the whole MRI follow-up, new lesions (enhancing and non-enhancing) were analyzed. RESULTS: A total of 129 patients were included in this study (65% female, mean age = 41 years, mean treatment duration 6.5 years, 50% positive for John Cunningham virus) and benefited from 735 MRIs with GBCA. Only 3 MRIs showed a new enhancing lesion, systematically encountered after treatment discontinuation. CONCLUSION: According to this study based on the clinical and radiological practice, the systematic use of GBCA seems of limited relevance in the MRI follow-up of asymptomatic patients treated continuously with natalizumab.

Magnetic resonance imaging of arterial stroke mimics: a pictorial review.

Acute ischaemic stroke represents the most common cause of new sudden neurological deficit, but other diseases mimicking stroke happen in about one-third of the cases. Magnetic resonance imaging (MRI) is the best technique to identify those 'stroke mimics'. In this article, we propose a diagnostic approach of those stroke mimics on MRI according to an algorithm based on diffusion-weighted imaging (DWI), which can be abnormal or normal, followed by the results of other common additional MRI sequences, such as T2 with gradient recalled echo weighted imaging (T2-GRE) and fluid-attenuated inversion recovery (FLAIR). Analysis of the signal intensity of the parenchyma, the intracranial arteries and, overall, of the veins, is crucial on T2-GRE, while anatomic distribution of the parenchymal lesions is essential on FLAIR. Among stroke mimics with abnormal DWI, T2-GRE demonstrates obvious abnormalities in case of intracerebral haemorrhage or cerebral amyloid angiopathy, but this sequence also allows to propose alternative diagnoses when DWI is negative, such as in migraine aura or headaches with associated neurological deficits and lymphocytosis (HaNDL), in which cortical venous prominence is observed at the acute phase on T2-GRE. FLAIR is also of major interest when DWI is positive by better showing evocative distribution of cerebral lesions in case of seizure (involving the hippocampus, pulvinar and cortex), hypoglycaemia (bilateral lesions in the posterior limb of the internal capsules, corona radiata, striata or splenium of the corpus callosum) or in posterior reversible encephalopathy syndrome (PRES). Other real stroke mimics such as mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS), Susac's syndrome, brain tumour, demyelinating diseases and herpes simplex encephalitis are also included in our detailed and practical algorithm. KEY POINTS: • About 30% of sudden neurological deficits are due to non-ischaemic causes. • MRI is the best technique to identify stroke mimics. • Our practical illustrated algorithm based on DWI helps to recognise stroke mimics.

Incident Cerebral Microbleeds Detected by Susceptibility Weight-Imaging Help to Identify Patients with Mild Cognitive Impairment Progressing to Alzheimer's Disease.

BACKGROUND: The relationship between cerebral microbleeds (CMB) and Alzheimer's disease (AD) has not yet been clearly determined, particularly with susceptibility weight-imaging (SWI). OBJECTIVE: To evaluate the SWI sequence using 3T MRI for the detection of CMB, and its ability to differentiate elderly control subjects (CS), stable mild cognitive impairment patients (MCI-s), MCI patients progressing to AD (MCI-p), and AD patients. METHODS: It was a prospective, monocentric, observational study that took place in Toulouse, France. Participants were 65 years and older, enrolled in three groups: CS, MCI, and AD. Based on the longitudinal analysis of cognitive decline, MCI subjects were retrospectively classified as MCI-s or MCI-p. Each patient had a 4-year follow-up with MRI at baseline (MRI#1) and during the fourth year (MRI#3). CMB were counted on native SWI images juxtaposed to minIP reformatted images. RESULTS: 150 patients were enrolled: 48 CS, 25 MCI-s, 18 MCI-p, 59 AD. At MRI#1 and at MRI#3, there was no significant difference in the prevalence of CMB between groups (p = 0.75 and p = 0.87). In the MCI-p + AD group, significantly more subjects had≥4 incident CMB compared to the CS + MCI-s group (p = 0.016). In the MCI-p + AD group, the prevalence of patients with >4 CMB was significantly higher at MRI#3 than at MRI#1 (p = 0.008). CONCLUSION: Using SWI, AD and MCI-p patients had developed significantly more new CMB than CS and MCI-s patients during the follow-up. Incident CMB might be suggested as a potential imaging marker of AD progression.

Cortical florbetapir-PET amyloid load in prodromal Alzheimer's disease patients.

BACKGROUND: Florbetapir (AV-45) has been shown to be a reliable tool to assess amyloid load in patients with Alzheimer's disease (AD) at demential stages. Longitudinal studies also suggest that AV-45 has the ability to bind amyloid in the early stages of AD. In this study, we investigated AV-45 binding and its relation with cognitive performance in a group of patients at the prodromal stage of Alzheimer's disease, recruited according to strict inclusion criteria. METHODS: We recruited patients at the prodromal stage of AD and matched control subjects. AV-45 binding was assessed using an innovative extraction method allowing quantifying uptake in the cortex only. AV-45 uptake was compared between groups in the precuneus, posterior cingulate, anterior cingulate, and orbito-frontal regions. Correlations between AV-45 uptake and cognitive performance were assessed. RESULTS: Twenty-two patients and 17 matched control subjects were included in the study. We report a significant increase of cortical AV-45 uptake in the patients compared to the control subjects in all regions of interest. Specific correlations were found within the patient group between mean global amyloid cortical load and cognitive performance in three different memory tests. CONCLUSIONS: These findings suggest that at the prodromal stage of AD, memory decline is linked to an increase of cortical ß-amyloid load.