Interlaboratory evaluation of Mucorales PCR assays for testing serum specimens: A study by the fungal PCR Initiative and the Modimucor study group.

Interlaboratory evaluations of Mucorales qPCR assays were developed to assess the reproducibility and performance of methods currently used. The participants comprised 12 laboratories from French university hospitals (nine of them participating in the Modimucor study) and 11 laboratories participating in the Fungal PCR Initiative. For panel 1, three sera were each spiked with DNA from three different species (Rhizomucor pusillus, Lichtheimia corymbifera, Rhizopus oryzae). For panel 2, six sera with three concentrations of R. pusillus and L. corymbifera (1, 10, and 100 genomes/ml) were prepared. Each panel included a blind negative-control serum. A form was distributed with each panel to collect results and required technical information, including DNA extraction method, sample volume used, DNA elution volume, qPCR method, qPCR template input volume, qPCR total reaction volume, qPCR platform, and qPCR reagents used. For panel 1, assessing 18 different protocols, qualitative results (positive or negative) were correct in 97% of cases (70/72). A very low interlaboratory variability in Cq values (SD = 1.89 cycles) were observed. For panel 2 assessing 26 different protocols, the detection rates were high (77-100%) for 5/6 of spiked serum. There was a significant association between the qPCR platform and performance. However, certain technical steps and optimal combinations of factors may also impact performance. The good reproducibility and performance demonstrated in this study support the use of Mucorales qPCR as part of the diagnostic strategy for mucormycosis.

Isavuconazole MIC distribution of 29 yeast species responsible for invasive infections (2015-2017).

OBJECTIVES: Isavuconazole is a recent extended-spectrum triazole with activity against yeasts. However, few data are available about the in vitro activity of rare yeast species. We report the MIC distribution of isavuconazole compared with fluconazole for a large collection of common or rare yeasts. METHODS: Isavuconazole and fluconazole MICs were determined using the EUCAST method for 1457 clinical isolates, mainly recovered from invasive infections, belonging to 29 species. They were sent to the National Reference Centre for Invasive Mycoses & Antifungals between January 2015 and October 2017 and species identification was performed using a polyphasic approach (matrix-assisted laser desorption/ionization time of flight analysis and a molecular method). RESULTS: Isavuconazole had effective in vitro activity against Cryptococcus neoformans (MIC90 < 0.25 mg/L), the five most common Candida spp. (MIC90 ≤ 0.5 mg/L for Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei) and also against the majority of rare species, including Candida kefyr and Candida lusitaniae. A few isolates of C. albicans (0.7%, 3/404), C. glabrata (2.7%, 5/184), C. tropicalis (1.0%, 1/96) and C. parapsilosis (0.8%, 1/127) exhibited MIC ≥4 mg/L. All were also resistant to fluconazole according to the EUCAST breakpoints. Some isolates with isavuconazole MIC ≥4 mg/L were also observed among rarer species: Meyerozyma guilliermondii (8.7%, 2/23), Wickerhamomyces anomalus (10.0%, 1/10). Other rare species Saprochaete clavata, Magnusiomyces capitatus, and Rhodotorula mucilaginosa had high MIC50 (≥1 mg/L) and MIC90 (≥4 mg/L) and could be considered as resistant to isavuconazole. CONCLUSIONS: We confirmed the good in vitro activity of isavuconazole against common Candida, Cryptococcus species and the majority of the rare yeast species studied.

From phaeohyphomycosis to disseminated chromoblastomycosis: A retrospective study of infections caused by dematiaceous fungi.

OBJECTIVE: Infections caused by dematiaceous fungi are more common in tropical and subtropical areas. We aimed to describe the clinical, microbiological and therapeutic aspects of case patients diagnosed at a University Hospital located on an Indian Ocean island. PATIENTS AND METHODS: We performed an observational retrospective study of infections caused by dematiaceous fungi diagnosed at the University Hospital of Saint-Pierre, Reunion, from 2000 to 2015. Mycological identifications were performed at the National Reference Center for Invasive Mycosis and Antifungal Agents (Paris). RESULTS: The review of clinical and microbiological data of 11 patients identified revealed that five were infected by dematiaceous fungi. Two had cutaneous phaeohyphomycosis, two had cerebral phaeohyphomycosis and one had cutaneous chromoblastomycosis with brain and potentially medullary dissemination. Skin lesions and cerebral abscesses were quite varied. CONCLUSION: Infections caused by dematiaceous fungi are rare. Medullary and brain localizations are extremely rare, especially for chromoblastomycosis. Cutaneous manifestations of phaeohyphomycosis are varied; diagnosis is thus more difficult. It is therefore important, when confronted with a chronic tumor-like lesion in endemic areas, to perform a biopsy for pathology and fungal culture. While surgical excision is not always sufficient, medical treatment of these infections is not standardized, but relies on an azole, which can be associated with another antifungal agent.

[Classical and molecular methods for identification and quantification of domestic moulds]. / Méthodes d'identification et de quantification des moisissures de l'habitat : méthodes classiques, méthodes moléculaires.

INTRODUCTION: To study the impact of the constant and inevitable inhalation of moulds, it is necessary to sample, identify and count the spores. BACKGROUND: Environmental sampling methods can be separated into three categories: surface sampling is easy to perform but non quantitative, air sampling is easy to calibrate but provides time limited information, and dust sampling which is more representative of long term exposure to moulds. The sampling strategy depends on the objectives (evaluation of the risk of exposure for individuals; quantification of the household contamination; evaluation of the efficacy of remediation). The mould colonies obtained in culture are identified using microscopy, Maldi-TOF, and/or DNA sequencing. VIEWPOINTS: Electrostatic dust collectors are an alternative to older methods for identifying and quantifying household mould spores. They are easy to use and relatively cheap. Colony counting should be progressively replaced by quantitative real-time PCR, which is already validated, while waiting for more standardised high throughput sequencing methods for assessment of mould contamination without technical bias. CONCLUSION: Despite some technical recommendations for obtaining reliable and comparable results, the huge diversity of environmental moulds, the variable quantity of spores inhaled and the association with other allergens (mites, plants) make the evaluation of their impact on human health difficult. Hence there is a need for reliable and generally applicable quantitative methods.

Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF).

The main objective of this study was to assess the diagnostic performance of a set of three Mucorales quantitative PCR assays in a retrospective multicentre study. Mucormycosis cases were recorded thanks to the French prospective surveillance programme (RESSIF network). The day of sampling of the first histological or mycological positive specimen was defined as day 0 (D0). Detection of circulating DNA was performed on frozen serum samples collected from D-30 to D30, using quantitative PCR assays targeting Rhizomucor, Lichtheimia, Mucor/Rhizopus. Forty-four patients diagnosed with probable (n = 19) or proven (n = 25) mucormycosis were included. Thirty-six of the 44 patients (81%) had at least one PCR-positive serum. The first PCR-positive sample was observed 9 days (range 0-28 days) before diagnosis was made using mycological criteria and at least 2 days (range 0-24 days) before imaging. The identifications provided with the quantitative PCR assays were all concordant with culture and/or PCR-based identification of the causal species. Survival rate at D84 was significantly higher for patients with an initially positive PCR that became negative after treatment initiation than for patients whose PCR remained positive (48% and 4%, respectively; p <10-6). The median time for complete negativity of PCR was 7 days (range 3-19 days) after initiation of l-AmB treatment. Despite some limitations due to the retrospective design of the study, we showed that Mucorales quantitative PCR could not only confirm the mucormycosis diagnosis when other mycological arguments were present but could also anticipate this diagnosis. Quantification of DNA loads may also be a useful adjunct to treatment monitoring.

Molecular identification of Mucorales in human tissues: contribution of PCR electrospray-ionization mass spectrometry.

Molecular methods are crucial for mucormycosis diagnosis because cultures are frequently negative, even if microscopy suggests the presence of hyphae in tissues. We assessed PCR/electrospray-ionization mass spectrometry (PCR/ESI-MS) for Mucorales identification in 19 unfixed tissue samples from 13 patients with proven or probable mucormycosis and compared the results with culture, quantitative real-time PCR, 16S-23S rRNA gene internal transcribed spacer region (ITS PCR) and 18S PCR sequencing. Concordance with culture identification to both genus and species levels was higher for PCR/ESI-MS than for the other techniques. Thus, PCR/ESI-MS is suitable for Mucorales identification, within 6 hours, for tissue samples for which microscopy results suggest the presence of hyphae.

Breakthrough invasive fungal disease in patients receiving posaconazole primary prophylaxis: a 4-year study.

Posaconazole (PSC) is currently recommended as primary prophylaxis in neutropenic patients with acute myeloid leukaemia (AML) and in allogenic haematopoietic stem cell transplantation (AHSCT) recipients with graft-versus-host disease (GVHD). Studies focusing on breakthrough invasive fungal disease (IFD) upon PSC prophylaxis show disparate results. In order to evaluate the incidence of IFD in patients on PSC prophylaxis and identify IFD risk factors, we carried out a retrospective study of all consecutive patients on PP from January 2007 to December 2010 in our hospital. Breakthrough IFDs were identified from the database of the central pharmacy and the French administrative database (PMSI), registering final medical diagnoses of hospitalized patients. Medical data were reviewed to study proven or probable IFD, according to EORTC/MSG definition. PSC plasma concentrations (PPC) were also retrieved. Poisson models were used for statistical analysis. Two hundred and seventy-nine patients received PSC prophylaxis for a median duration of 1.4 months (range 0.2-17.9). Proven (n=6) or probable (n=3) IFDs were diagnosed in nine cases (3.2%). IFD incidence rate per 100 person-month was 1.65 (95% CI, 0.79-2.97). IFDs were candidaemia (Candida glabrata, n=2), pulmonary invasive aspergillosis (n=3), disseminated fusariosis (n=2) and pulmonary mucormycosis (n=2). Seven deaths were reported, directly related to IFD in three patients (33.3%). First dosage of PPC under 0.3 mg/L was the single significant risk factor for IFD (RR, 7.77; 95% CI, 1.30-46.5; p 0.025). Breakthrough IFD in patients receiving PSC prophylaxis is rare but associated with a poor outcome. Low PSC plasma concentrations are associated with an increased risk of IFD.

Iterative breakthrough invasive aspergillosis due to TR(34) /L98H azole-resistant Aspergillus fumigatus and Emericella sublata in a single hematopoietic stem cell transplant patient.

We report 3 consecutive episodes of invasive aspergillosis in a single hematopoietic stem cell transplant patient successively attributed to TR(34) /L98H azole-resistant Aspergillus fumigatus and to a first occurrence of invasive Emericella sublata infection. This case illustrates potential selection of resistant molds during antifungal therapy in hematological patient.

Difficulties with molecular diagnostic tests for mould and yeast infections: where do we stand?

PCR assays have not reached the same level of acceptance for the detection of human fungal pathogens as for other micro-organisms, mainly because the low number of micro-organisms challenges the detection limits of PCR. Therefore, whereas meta-analyses focusing on clinical validation suggest interest in adding PCR results to the diagnostic workup for invasive fungal disease (IFD) along with clinical evaluation, CT scans, classical mycology and antigen detection, no consensual PCR method has emerged. Compared with the end-point format of the 1990s, real-time quantitative PCR is a major breakthrough. This format prevents contamination with previously amplified products, provides the yield of amplification, allows for developing consensus procedures and should therefore be the only format used. An internal control is now mandatory to avoid false-negative results. Primer design strongly impacts on the objectives: pan-fungal primers can provide false-positive results due to environmental fungal DNA contamination; conversely, species-specific primers miss infections caused by untargeted fungi. Unresolved issues include the best specimens to be used; serum is currently preferred to blood because of the ease of the DNA extraction step. Work is in progress to establish standards at least for Aspergillus PCR, and the implementation of quality controls should help centres to improve assays. Eventually, the classical analysis of biomarker performance does not consider the evolving risk factors and changing treatments during IFD, which can lead to variable conclusions. New statistical methods such as event history analysis should be considered.

Antifungal pre-emptive strategy for high-risk neutropenic patients: why the story is still ongoing.

Neutropenic patients with haematological malignancies are at high risk of invasive fungal disease (IFD). Due to limitations in specific procedures to establish an early diagnosis of IFD, two historical unpowered studies suggested, three decades ago, that giving an empirical antifungal treatment to patients with persistent or recurrent fever under broad-spectrum antibacterials, could reduce the risk of IFD. For cost and toxicity reasons, this strategy became debated when modern imaging and indirect biological markers became available. Different pre-emptive strategies, either based on lung imaging, galactomannan antigenaemia, fungal PCR, or a combination of several parameters, were designed with the goal of restricting the administration of antifungals to the more at-risk patients with early signs of IFD. Almost all pre-emptive studies showed or suggested a reduction of administration and cost of antifungals during neutropenic phases. However, the clinical pertinence and safety of the strategy, and mainly its optimal design, are still pending. This paper reviews the evolution of these strategies and how they may be implemented in the haematology ward.

Diagnosis, management and outcome of Candida endocarditis.

Limited data exist on Candida endocarditis (CE) outcome in the era of new antifungals. As early diagnosis of CE remains difficult, non-culture-based tools need to be evaluated. Through the French prospective MYCENDO study (2005-2007), the overall characteristics and risk factors for death from CE were analysed. The contribution of antigen detection (mannan/anti-mannan antibodies and (1,3)-ß-d-glucans) and molecular tools was evaluated. Among 30 CE cases, 19 were caused by non-albicans species. Sixteen patients (53%) had a predisposing cardiac disease, which was a valvular prosthesis in ten (33%). Nine patients (30%) were intravenous drug users; none of them had right-sided CE. Among the 21 patients who were not intravenous drug users, 18 (86%) had healthcare-associated CE. Initial therapy consisted of a combination of antifungals in 12 of 30 patients (40%). Thirteen patients (43%) underwent valve replacement. The median follow-up was 1 year after discharge from hospital (range, 5 months to 4 years) and hospital mortality was 37%. On univariate analysis, patients aged ≥60 years had a higher mortality risk (OR 11, 95% CI 1.2-103.9; p 0.024), whereas intravenous drug use was associated with a lower risk of death (OR 0.12, 95% CI 0.02-0.7; p 0.03). Among 18 patients screened for both serum mannan/anti-mannan antibodies and (1,3)-ß-d-glucans, all had a positive result with at least one of either test at CE diagnosis. Real-time PCR was performed on blood (SeptiFast) in 12 of 18, and this confirmed the blood culture results. In conclusion, CE prognosis remains poor, with a better outcome among younger patients and intravenous drug users. Detection of serum antigens and molecular tools may contribute to earlier CE diagnosis.

ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients.

As culture-based methods for the diagnosis of invasive fungal diseases (IFD) in leukemia and hematopoietic SCT patients have limited performance, non-culture methods are increasingly being used. The third European Conference on Infections in Leukemia (ECIL-3) meeting aimed at establishing evidence-based recommendations for the use of biological tests in adult patients, based on the grading system of the Infectious Diseases Society of America. The following biomarkers were investigated as screening tests: galactomannan (GM) for invasive aspergillosis (IA); ß-glucan (BG) for invasive candidiasis (IC) and IA; Cryptococcus Ag for cryptococcosis; mannan (Mn) Ag/anti-mannan (A-Mn) Ab for IC, and PCR for IA. Testing for GM, Cryptococcus Ag and BG are included in the revised EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) consensus definitions for IFD. Strong evidence supports the use of GM in serum (A II), and Cryptococcus Ag in serum and cerebrospinal fluid (CSF) (A II). Evidence is moderate for BG detection in serum (B II), and the combined Mn/A-Mn testing in serum for hepatosplenic candidiasis (B III) and candidemia (C II). No recommendations were formulated for the use of PCR owing to a lack of standardization and clinical validation. Clinical utility of these markers for the early management of IFD should be further assessed in prospective randomized interventional studies.

Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005-2007).

A prospective (2005-2007) hospital-based multicentre surveillance of EORTC/MSG-proven or probable invasive aspergillosis (IA) cases whatever the underlying diseases was implemented in 12 French academic hospitals. Admissions per hospital and transplantation procedures were obtained. Cox regression models were used to determine risk factors associated with the 12-week overall mortality. With 424 case-patients included, the median incidence/hospital was 0.271/10(3) admissions (range 0.072-0.910) without significant alteration of incidence and seasonality over time. Among the 393 adults (62% men, 56 years (16-84 years)), 15% had proven IA, 78% haematological conditions, and 92.9% had lung involvement. Acute leukaemia (34.6%) and allogeneic stem cell transplantation (21.4%) were major host factors, together with chronic lymphoproliferative disorders (21.6%), which emerged as a new high-risk group. The other risk host factors consisted of solid organ transplantation (8.7%), solid tumours (4.3%), systemic inflammatory diseases (4.6%) and chronic respiratory diseases (2.3%). Serum galactomannan tests were more often positive (≥69%) for acute leukaemia and allogeneic stem cell transplantation than for the others (<42%; p <10(-3)). When positive (n = 245), cultures mainly yielded Aspergillus fumigatus (79.7%). First-line antifungal therapy consisted of voriconazole, caspofungin, lipid formulations of amphotericin, or any combination therapy (52%, 14%, 8% and 19.9%, respectively). Twelve-week overall mortality was 44.8% (95% CI, 39.8-50.0); it was 41% when first-line therapy included voriconazole and 60% otherwise (p <0.001). Independent factors for 12-week mortality were older age, positivity for both culture and galactomannan and central nervous system or pleural involvement, while any strategy containing voriconazole was protective.

Black grain mycetoma caused by Leptosphaeria tompkinsii.

Leptosphaeria tompkinsii is a dematiaceous fungus which is rarely reported as an agent of black-grain mycetoma. We present a case involving a mycetoma of the hand of a former farmer from Mali, West Africa, who has been a resident in France for 27 years. The patient was successfully treated with surgery and the use of oral itraconazole for 6 months. Species identification was based on sexual reproductive structures observed on potato-carrot agar media and the use of internal transcribed spacer sequencing.

Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.

BACKGROUND: Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). OBJECTIVE: To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. METHODS: A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease. RESULTS: 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002). CONCLUSION: Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.

A retrospective series of gut aspergillosis in haematology patients.

Gut invasive aspergillosis is an extremely rare infection in immunocompromised patients. The goal of this retrospective multicentre study is to report on cases of gut aspergillosis in haematology patients, including clinical presentation, risk factors, and outcome. Twenty-one patients from nine centres were identified. Eight had isolated gut aspergillosis, with no evidence of other infected sites, and 13 had disseminated aspergillosis. Thirteen patients had acute leukaemia. Nine were allogeneic stem cell transplant recipients. Clinical symptoms and imaging were poorly specific. The galactomannan antigenaemia test result was positive in 16/25 (64%) patients, including in four of the eight cases of isolated gut aspergillosis. Five of 21 patients had a dietary regimen rich in spices, suggesting that, in these cases, food could have been the source of gut colonization, and then of a primary gut Aspergillus lesion. The diagnosis was made post-mortem in six patients. The mortality rate in the remaining patients at 12 weeks was 7/15 (47%). Gut aspergillosis is probably misdiagnosed and underestimated in haematology patients, owing to the poor specificity of symptoms and imaging. Patients with a persistently positive galactomannan antigenaemia finding that is unexplained by respiratory lesions should be suspected of having gut aspergillosis in the presence of abdominal symptoms, and be quickly investigated. In the absence of severe abdominal complications leading to surgery and resection of the lesions, the optimal treatment is not yet defined.

Yeast contamination of kidney, liver and cardiac preservation solutions before graft: need for standardisation of microbial evaluation.

Contamination of preservation solution (PS) with yeasts during solid organ recovery can lead to life-threatening complications in the recipients. The prevalence of such a contamination needs to be established. From January 2004 to December 2008, we prospectively investigated the potential fungal contamination of all the PSs collected in our institution using a standardised procedure consisting in centrifugation of 10 mL PS and incubation of the pellet seeded on fungal-specific medium for 15 days at 30 degrees C. During the study period, 728 transplantations (397 kidneys, 262 livers and 69 hearts) were performed for which 659 PSs (90.5%) were available. The yeast contamination rate was 0% (0/62), 3.1% (11/356) and 4.1% (10/241) for heart, kidney and liver transplants, respectively. We identified 10 Candida albicans, five C. glabrata, two C. krusei, one C. tropicalis, one C. valida, one Pichia etchelsii and one Rhodorula sp. Routine bacterial analysis identified only five of these 21 fungal contaminations. Twenty recipients were alive after at least one year of follow-up and one died from meningeal carcinomatosis at seven months. Three patients were found to have the same species of Candida from their surgical drains but did not develop any infection or abnormalities upon ultrasound investigation. Fourteen patients received antifungal drugs. Yeast contamination occurred in 3.4% of all kidney and liver PSs tested. Its clinical consequences and therapeutic management remain to be defined. Our study also suggests that optimisation/standardisation of microbiological procedures is warranted, including analysis of large PS volume, seeding of fungal-specific medium and prolonged incubation.

Comparison of antifungal MICs for yeasts obtained using the EUCAST method in a reference laboratory and the Etest in nine different hospital laboratories.

In routine laboratory practice, the determination of MICs of antifungals for yeasts often relies on the Etest, because of a good correlation with reference methods. However, this correlation was established through predesigned studies, rather than prospective testing. The surveillance programme of fungaemia (YEASTS programme), implemented since 2003, facilitated our comparison of the Etest and the EUCAST results, obtained on a routine basis in nine different hospitals and in a reference laboratory, respectively. The analysis included 690 isolates recovered from blood culture (362 Candida albicans, 113 Candida glabrata, 69 Candida parapsilosis, 55 Candida tropicalis, 31 Cryptococcus neoformans, and 60 other yeast species) that were tested for their susceptibility to amphotericin B (n = 655), fluconazole (n = 669), itraconazole (n = 198), voriconazole (n = 588), flucytosine (n = 314), and caspofungin (n = 244). Agreement between the Etest and EUCAST datasets was calculated and categorized on the basis of previously published breakpoints. The level of agreement at ±2 dilutions was 75% for amphotericin B and 90% for flucytosine; for the azoles, it ranged from 71% for itraconazole to 87% for voriconazole. No significant difference was observed among the yeast species, except for Cryptococcus neoformans and flucytosine, with an agreement <40%. Categorical agreement ranged from 60% for itraconazole to 90% for flucytosine. Major and very major discrepancies occurred in <12% and 6%, respectively. The Etest, even when performed on a routine basis, shows a ≥71% agreement with the EUCAST reference method.

[Brain MRI associated with chronic hepatic failure and hypermanganism]. / Hypersignal T1 bipallidal dans le cadre d'une cirrhose avec hypermanganésémie.

INTRODUCTION: Hypermanganism is primarily linked to inhalation exposure. Several observations of exogenous manganese poisoning have been reported associating neuropsychiatric symptoms, parkinsonian syndrome and hyperintensities of the two pallida on T1 weighted sequences on brain MRI. Recently, similar neurological and radiological signs have been described without exogenous exposure to manganese but in the framework of endogenous poisoning particularly in chronic hepatic failure. CASE REPORT: We report the case of a 41-year-old HIV-positive and HVC-positive man who presented psychomotor impairment associated with bipallidal T1 hyperintensities on the brain MRI. The diagnosis of a hypermanganesemia was made on blood samples. We present a literature review on exogenous and endogenous hypermanganesemia and discuss differential diagnosis in the radiological setting of bipallidal T1 hyperintensities. CONCLUSION: Bipallidal T1 hyperintensities on brain MRI may suggest hypermanganism even in the clinical setting of a non-specific neurological disorder such as psychomotor impairment.