Delineation of cellular stages and identification of key proteins for reduction and biotransformation of Se(IV) by Stenotrophomonas bentonitica BII-R7.

The widespread use of selenium (Se) in technological applications (e.g., solar cells and electronic devices) has led to an accumulation of this metalloid in the environment to toxic levels. The newly described bacterial strain Stenotrophomonas bentonitica BII-R7 has been demonstrated to reduce mobile Se(IV) to Se(0)-nanoparticles (Se(0)NPs) and volatile species. Amorphous Se-nanospheres are reported to aggregate to form crystalline nanostructures and trigonal selenium. We investigated the molecular mechanisms underlying the biotransformation of Se(IV) to less toxic forms using differential shotgun proteomics analysis of S. bentonitica BII-R7 grown with or without sodium selenite for three different time-points. Results showed an increase in the abundance of several proteins involved in Se(IV) reduction and stabilization of Se(0)NPs, such as glutathione reductase, in bacteria grown with Se(IV), in addition to many proteins with transport functions, including RND (resistance-nodulation-division) systems, possibly facilitating Se uptake. Notably proteins involved in oxidative stress defense (e.g., catalase/peroxidase HPI) were also induced by Se exposure. Electron microscopy analyses confirmed the biotransformation of amorphous nanospheres to trigonal Se. Overall, our results highlight the potential of S. bentonitica in reducing the bioavailability of Se, which provides a basis both for the development of bioremediation strategies and the eco-friendly synthesis of biotechnological nanomaterials.

Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents.

OBJECTIVES: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. METHODS: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. RESULTS: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/105 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/105 (+126%; P<0.001) and for UC, from 1.6 to 4.1/105 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. CONCLUSIONS: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

INRS activities on risk assessment of glycol ethers.

The occupational exposure assessment uses data from published sources, from Industry (most often from the producers), and from dedicated occupational exposure data bases, as well as evaluations using the EASE model (Estimation and Assessment of Substance Exposure). Atmospheric concentrations and characteristics of skin contacts are evaluated in different scenarios (such as manufacturing, formulating, main and most polluting uses) and sub-scenarios (e.g. warm water dilution). Air concentrations of EGBE are low during production (most often <0.5 mg/m(3)), incidental excursions being <50 mg/m(3); the "worst-case" mean concentration is proposed as 9 mg/m(3). Skin contact, according to EASE, may be in the range of 0-0.1 mg/cm(2)(day), and should be mitigated by the use of suitable gloves. For formulations of products containing EGBE, air concentrations are evaluated as 10 mg/m(3) and skin contact as 0.19 mg/cm(2)(day). The "reasonable worst case" air concentrations (8-Hr TWA) are assessed at around 11 mg/m(3) (coating industry), from 5 to 20 mg/m(3) in printing activities (depending on the task), and in the 20-70 mg/m(3) range (upper limit 40 mg/m(3) in better controlled situations) for cleaning activities. Skin contact would be around twice the preceding level, i.e., 0.4 mg/cm(2)(day) for coating as well as cleaning activities. EGBE and its major metabolites, 2-butoxyacetaldehyde (2-BAL) and 2-butoxyacetic acid (2-BAA) have been subjected to tests for genetic toxicity tests both in vitro and in vivo. While some positive responses have been obtained, the balance of the evidence indicates that EGBE does not express significant genotoxic activity. There are no epidemiological data investigating a relationship between exposure to EGBE and human cancer. Two carcinogenicity inhalation bioassays have been conducted in rodents, one in rats and one in mice. Significant increases were found in forestomach tumours in female mice and haemangiosarcomas in male mice. No increases in tumour incidences were found in either male or female rats. Mechanistic studies have suggested the crucial involvement in the pathogenesis of haemangiosarcomas of a chain of events consisting of (1) haemolysis due to BAA, followed by (2) hepatic haemosiderin deposition and (3) the subsequent generation of reactive oxygen species within the endothelial cells from which haemangiosarcomas arise. Since human erythrocytes are particularly resistant to the haemolytic effects of BAA, it is extremely unlikely, according to this model, that the haemangiosarcomas observed in male mice will have human significance. Similarly, mechanistic studies on the female mouse forestomach tumours have suggested that these also are not important as an indication of human risk. In vivo, EGBE tested in a continuous breeding study and in repeated dose toxicity tests, did not produced specific effects on reproductive organs or fertility parameters. For developmental toxicity, rats, mice and rabbits were dosed via oral and/or inhalation routes. Foeto- and embryo-toxicity was observed in presence or maternal toxicity (haemolytic anaemia). The data available give plausible support to the hypothesis that this developmental toxicity is a direct consequence of maternal toxicity. There are no epidemiological data investigating a relationship between exposure to EGBE alone and human reproductive effects.

A homogeneous caspase-3 activity assay using HTRF technology.

Caspases are cysteine proteases presenting a conserved active site that cleaves protein substrates at a highly specific position. They are involved in different aspects of the active cell death pathway. Most of them act through proteolytic degradations of cellular components. This paper describes the assay development, assay validation, and screening for inhibitors of this enzyme, which could be potential drug candidates. The assay uses homogeneous time-resolved fluorescence based on energy transfer from europium cryptate as donor to cross-linked allophycocyanin as acceptor (XL665). A double-tagged substrate, biotinyl-epsilon-aminocaproyl-L-aspartyl-L-glutamyl-L-valyl-Laspartyl-L-alanyl-L-propyl-N(epsilon)-(2,4-dinitrophenyl)-L-lysine-amide (biotin-X-DEVDAPK(dnp)-NH(2)), is conjugated with streptavidin cryptate and anti-dnp-XL665 monoclonal antibody. The close proximity between donor and acceptor induces a specific time-resolved fluorescence signal. In the presence of enzyme activity, the substrate cleavage induces an unlinking of the two fluorescent probes and, subsequently, the disappearance of the specific signal as a result of loss of proximity. Experiments to optimize the reagent concentration, incubation times, precision, reproducibility, and robustness are discussed in comparison with a fluorometric method.

Europium cryptate labeled deoxyuridine-triphosphate analog: synthesis and enzymatic incorporation.

The synthesis of an europium tris-bipyridine cryptate labeled 2'-deoxyuridine-5 '-triphosphate analog (K-11-dUTP) is described. This labeled triphosphate was incorporated into DNA through enzymatic reactions with terminal transferase and DNA polymerases. The enzymatic reactions were monitored by TRACE (Time Resolved Amplification of Cryptate Emission), a homogeneous method using Fluorescence Resonance Energy Transfer (FRET) from an europium cryptate as donor to a modified allophycocyanine as acceptor.

Europium cryptate-tethered ribonucleotide for the labeling of RNA and its detection by time-resolved amplification of cryptate emission.

TRACE (time-resolved amplification of cryptate emission), also called HTRF for pharmaceutical applications, is a homogeneous time-resolved fluorescence technique well adapted for the study of molecular interactions. It is based on fluorescence resonance energy transfer (FRET) between europium trisbipyridine cryptate (TBPEu(3+)) as energy donor and cross-linked allophycocyanin, symbolized by XL665, as acceptor, leading to a long-lived FRET signal. TBPEu(3+)-labeled uridine triphosphate (UTP), referred to as K-11-UTP in the text, was obtained by coupling TBPEu(3+) moiety to a C-5 functionalized UTP analog. K-11-UTP can be directly incorporated in RNA strands during enzymatic synthesis. This was demonstrated in an in vitro transcription reaction promoted by T(7) RNA polymerase. The reaction was performed in the presence of K-11-UTP and biotin-labeled cytidine triphosphate (biotin-16-CTP) in admixture with natural ribonucleotides. After the addition of streptavidin-XL665 conjugate (SA-XL665), which binds on biotinylated cytidine residues, a long-lived FRET signal was obtained. This proved that both europium cryptate and biotin were incorporated into the same RNA strand and are close enough to generate a FRET signal. The study of this FRET detection assay format showed that such doubly labeled RNA can be easily detected even when a very low percentage of K-11-UTP is used (less than 1% of total UTP concentration). Europium-cryptate-labeled RNA can also be monitored using a homogeneous hybridization assay format involving a biotinylated probe. After the addition of SA-XL665, the FRET signal generated demonstrates the formation of RNA:DNA hybrids. Europium-cryptate-labeled nucleotide thus gives access to a new type of RNA nonisotopic labeling and homogeneous detection assays.

[Study of hemispheric lateralization of language regions by functional MRI. Validation with the Wada test]. / Etude de latéralisation hémisphérique des aires du langage en IRM fonctionnelle. Validation par le test de Wada.

Language hemispheric dominance can be assessed by the Wada test before temporal lobectomy, in patients with refractory epilepsy of the mesial temporal lobe. Functional MR is a less invasive technique which recently demonstrated the ability to localize some language areas. The aim of this study was to determine if functional MR can be substituted to the Wada test in the determination of language dominance. Seven patients with a refractory epilepsy of the mesial temporal lobe were included. The MR protocol was carried out using a 1.5 T system including 12 axial gradient echo BOLD EPI images. A semantic fluency task, interspersed with rest periods, was used as activation paradigm. An activation of middle and inferior frontal region was found in all patients. It predominated in the left hemisphere in 6 cases and in the right hemisphere in 1 case. The hemispheric and frontal lobe lateralization of the functional MR activation was correlated with the hemispheric language dominance as assessed by the Wada test. In conclusion, functional MR is a promising technique in the determination of language dominance.

Functional MR evaluation of temporal and frontal language dominance compared with the Wada test.

OBJECTIVE: To evaluate the reliability of temporal and frontal functional MRI (fMRI) activation for the assessment of language dominance, as compared with the Wada test. PATIENTS AND METHODS: Ten patients with temporal lobe epilepsy were studied using blood oxygen level dependent fMRI and echoplanar imaging (1.5-T). Three tasks were used: semantic verbal fluency, covert sentence repetition, and story listening. Data were analyzed using pixel by pixel autocorrelation and cross-correlation. fMRI laterality indices were defined for several regions of interest as the ratio (L - R)/(L + R), L being the number of activated voxels in the left hemisphere and R in the right hemisphere. Wada laterality indices were defined as the difference in the percentages of errors in language tests between left and right carotid injections. RESULTS: Semantic verbal fluency: The asymmetry of frontal activation was correlated with Wada laterality indices. The strongest correlation was observed in the precentral/middle frontal gyrus/inferior frontal sulcus area. Story listening: The asymmetry of frontal, but not temporal, activation was correlated with Wada laterality indices. Covert sentence repetition: No correlation was observed. CONCLUSIONS: There was a good congruence between hemispheric dominance for language as assessed with the Wada test and fMRI laterality indices in the frontal but not in the temporal lobes. The story listening and the covert sentence repetition tasks increased the sensitivity of detection of posterior language sites that may be useful for brain lesion surgery.

Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Trilège (Agence Nationale de Recherches sur le SIDA 072) Study Team).

CONTEXT: In the Trilège trial, following induction with a zidovudine, lamivudine, and indinavir regimen, human immunodeficiency virus (HIV) replication was less suppressed by 2-drug maintenance therapy than by triple-drug therapy. OBJECTIVE: To identify mechanisms of virologic failure in the 3 arms of the Trilège trial. DESIGN: Case-control study conducted from February to October 1998. SETTING: Three urban hospitals in Paris, France. PATIENTS: Fifty-eight case patients with virologic failure (HIV RNA rebound to >500 copies/mL in 2 consecutive samples) randomized to 3 therapy groups: triple drug (zidovudine, lamivudine, and indinavir), 8; zidovudine-lamivudine, 29; and zidovudine-indinavir, 21; the case patients were randomly matched with 58 control patients with sustained viral suppression. MAIN OUTCOME MEASURES: At virologic failure (S1 sample) and 6 weeks later (S2 sample), assessment of protease and reverse transcriptase gene mutations, plasma indinavir level, and degree of viral load rebound; pill count during induction and maintenance periods. RESULTS: Only 1 primary resistance mutation, M184V, was detected in S1 plasma samples from 4 of 6 patients in the triple-drug and in all 22 in the zidovudine-lamivudine therapy groups and in S2 plasma samples from 3 of 6 in the triple-drug and 20 of 21 in the zidovudine-lamivudine groups. Of controls, M184V was detected in 11 of 13 S1 plasma samples and in 10 of 11 S2 plasma samples. Indinavir levels were undetectable in all S1 samples but 2 in 7 triple-drug cases tested and in the expected range in 11 of 18 S1 and 5 of 12 S2 zidovudine-indinavir case plasma samples tested. Maintenance adherence rates were lower for cases vs controls for zidovudine (P = .05) and indinavir (P = .05). Low indinavir levels, lower adherence rates for zidovudine (P = .04) and lamivudine (P = .03), and rebound to near-baseline values suggested adherence as cause of early failure for 4 of 8 triple-drug cases. In the zidovudine-lamivudine arm, for which case and control adherence rates did not differ significantly (P = .96), most failures occurred late with low rebound, suggesting suboptimal drug potency. In the zidovudine-indinavir arm, virologic failures may be related to both mechanisms. CONCLUSIONS: During the maintenance phase early and late virologic failures appeared to be related more to problems of adherence and antiretroviral treatment potency, respectively, than to selection of resistant mutant viruses.

Specificity of memory deficits after right or left temporal lobectomy.

An impairment of verbal memory has consistently been associated with resection of the left dominant temporal lobe, whereas non-verbal memory deficits have been less reliably observed following resection of the right temporal lobe. Such a dissociation may be due to material-specific differences of processing between verbal and non-verbal information. Alternatively, the influence of the left and right limbic structures may vary according to the stage of memory processing. The aim of the study was to test these hypotheses by comparing verbal and spatial learning in patients with left or right temporal lobe resection for intractable epilepsy, using verbal and visuospatial memory tasks with the same design: control of encoding, multiple trial learning, free and cued recall, short and long delays. The results showed: (1) a similar pattern of learning and recall in the two groups; (2) a higher performance in spatial learning for patients with left temporal lobe resection and in verbal learning for patients with right temporal lobe resection; (3) material-specific effects characterized by a higher sensitivity to cues in the verbal domain and a better retention of information during delays in the spatial domain. These results suggest parallel processing of the two temporal lobes at the various memory stages, rather than an interaction between memory stage and side of the lesion similar to that already proposed for the frontal lobes. They also confirm a double dissociation between verbal/spatial information processing and side of temporal lobe resection.

Bilateral mesial temporal sclerosis: MRI with high-resolution fast spin-echo and fluid-attenuated inversion-recovery sequences.

We report a retrospective analysis of MRI in 206 patients with intractable seizures and describe the findings in bilateral mesial temporal sclerosis (MTS) on fast spin-echo (FSE) and fast fluid-attenuated inversion-recovery (fFLAIR) sequences. Criteria for MTS were atrophy, signal change and loss of the digitations of the head of the hippocampus. In patients with bilateral MRI signs of MTS, correlation with clinical electro, volumetric MRI data and neuropsychological tests, when available, was performed. Bilateral MTS was observed in seven patients. Bilateral loss of the digitations and signal change on fFLAIR was seen in all seven. In three, bilateral atrophy was obvious. In two patients, mild bilateral atrophy was observed and in two others, the hippocampi were: asymmetrical, with obvious atrophy on only one side. Volumetric data confirmed bilateral symmetrical atrophy in five patients, and volumes were at the lowest of the normal range in the other two. The EEG showed temporal abnormalities in all patients, unilateral in five and bilateral in two. All patients had memory impairment and neuropsychological data confirmed visual and verbal memory deficits; two patients failed the Wada test on both sides. High-resolution T2-weighted FSE and fFLAIR sequences allow diagnosis of bilateral MTS, which has important therapeutic and prognostic implications.

Is the underlying cause of epilepsy a major prognostic factor for recurrence?

BACKGROUND: We investigated the prognostic value of the type of epilepsies and epileptic syndromes for seizure recurrence. In patients with partial epilepsy, we focused on the prognostic value of any structural brain abnormality and of the location of the epileptogenic region. METHODS: A total of 2,200 adult outpatients were included in a hospital-based observational survey, with a follow-up of 1 to 7 years. Twenty-two percent of the patients exhibited generalized epilepsy, 62% partial epilepsy, and 16% undetermined epilepsy. RESULTS: Seizure control (>1 year without seizure) was achieved in 82% of patients who had idiopathic generalized epilepsy, 35% of those with symptomatic partial epilepsy, 45% of those with cryptogenic partial epilepsy, and 11% of those with partial epilepsy associated with hippocampal sclerosis (HS). Temporal lobe epilepsy (TLE) was the most refractory partial epilepsy, with only 20% of such patients remaining seizure free, compared with 36% of extra-TLE patients. In partial epilepsy, HS, cerebral dysgenesis, and dual pathology (HS and another lesion) were associated with a low rate of seizure-free patients (11%, 24%, and 3%, respectively). No significant difference in seizure control was found between patients with extra-TLE and those with TLE and no HS. CONCLUSIONS: In adults, partial epilepsy is more difficult to treat than idiopathic generalized epilepsy. In patients who have partial epilepsy, the location of the epileptogenic zone does not seem to be a determining factor. Brain abnormalities--especially HS, either alone or associated with another lesion--are a major prognostic factor.

A randomised trial of mode of delivery in women infected with the human immunodeficiency virus.

OBJECTIVE: During the pilot phase of a trial to evaluate the effectiveness of caesarean section delivery compared with vaginal delivery in reducing mother-to-child transmission of human immunodeficiency virus (HIV) infection, the feasibility of randomisation to mode of delivery was assessed. DESIGN: At 36 weeks of pregnancy, women infected with HIV were randomly allocated to either caesarean section delivery at 38 weeks or vaginal delivery. Information was also collected on the reasons why women were not enrolled, either because they refused or had a contraindication. SETTING: Fifty-one centres in six European countries. POPULATION: Pregnant women with confirmed HIV-1 infection. MAIN OUTCOME MEASURES: Randomisation. RESULTS: Three-hundred and thirty-nine women had been randomised by the end of 1996, the large majority from Italy (n = 250) and France (n = 54), with 22 from South Africa, three from Sweden, nine from Barcelona and one from London. A further 150 women were eligible but had not been randomised. Forty-eight women (14%) were not delivered according to the arm to which they were randomised; the majority (n = 44) were changed from vaginal to caesarean section delivery. There is wide variation between European countries in the acceptability and adherence to the mode of delivery trial. CONCLUSION: The pilot phase of this trial has shown that in some settings randomisation to mode of delivery is feasible and acceptable, but that in other settings clinicians and pregnant women are more reluctant to be randomised. Pending further information on transmission rates and accrual, enrollment into the trial continues.

Chloride secretion drives urine formation in leech nephridia.

The transport mechanisms underlying urine formation in leech nephridia were investigated in situ and in isolated preparations using pharmacological, electrophysiological and micropuncture techniques. Canalicular cells, which secrete the primary urine, function as a Cl(-)-secreting epithelium. An apical Cl- conductance contributes to the lumen-negative potential which drives transcellular K+ transport and paracellular Na+ transport. On the basolateral side, a ouabain-sensitive Na+/K(+)-ATPase contributes substantially to the cellular and transcellular potential and provides the Na+ gradient necessary for a bumetanide-sensitive Na+/K+/2Cl- cotransport. Final urine is formed by subsequent reabsorption of ions along the central canal, where KCl and NaCl are reabsorbed in different portions. The postprandial diuresis is not a consequence of the changes in blood osmolality or ion concentrations. Similar changes in the ionic environment do not promote diuresis in isolated nephridia. Apparently, the composition and volume of the primary urine cannot be separately controlled. Any increase in fluid secretion by leech canalicular cells involves upregulation of the paracellular pathway and stimulation of Cl- entry, which thereby changes the normally K(+)-enriched primary urine to the Na(+)-enriched primary urine characteristic of leeches in diuresis.

Mass screening programs for breast cancer in France--average values of assessment criteria.

Breast cancer is the most common cancer in women worldwide. Many studies have been performed worldwide to assess the effectiveness of screening in terms of reduced mortality due to breast cancer. Since the end of 1989, 10 breast cancer mass screening programs using mammography have been carried out in France under the sponsorship of the National Fund for Health Prevention, Education, and Information (FNPEIS) from the National Health Insurance of Salaried Workers (CNAMTS). These 10 campaigns, which are on a district scale, are organized according to variable methods and are assessed using a common procedure. Four groups of criteria are measured in this procedure, which investigates the impact, quality, effectiveness, and costs of screening programs. The average and extreme values of each criterion as calculated from the campaigns are presented in this paper. In order to enlighten the judgment on the French results, a comparison with the international standards in force and with the results of foreign screening programs is proposed.

Use of mammography as a breast cancer screening tool in six districts in France.

Mass screening programs to detect breast cancer are currently under way in many countries. In France, several districts have been running mammographic screening programs since 1989. A survey was conducted in five of these districts and in a sixth district where no screening program was implemented. Using a self-addressed questionnaire mailed to a sample of 1500 women aged over 20 years, the survey was aimed at assessing women's use of mammography as well as their knowledge and perception of mammographic breast cancer screening. According to district, the compliance of the women replying to the questionnaire ranged from 72 to 82%. The proportion of women who had at least one mammography during their life ranged from 41 to 54%, according to district. The percentage of women aged 50 to 69 who had one mammography within 3 years before the survey ranged from 57 to 78% in the experimental districts and was only 48% in the control district. In all districts, women did not know exactly at what age it is recommended to start screening and with what periodicity, but, when invited to do so, they were satisfied with the program and intended to participate again.

[Mass screening programs for breast cancer in France. Comparative evaluation]. / Les programmes de dépistage de masse du cancer du sein en France. Evaluation comparative.

OBJECTIVE: The purpose of this work was to comparatively assess the results of mass screening programs for breast cancer implemented in six French departments in 1986, within the scope of the National Fund for Health Prevention, Education and Information of the National Health Insurance Office of Salaried Workers. MATERIAL AND METHODS: The data collected by the screening centres were analyzed by ten assessment teams that were independent from the program promotion staff, all using the same evaluation form. A complementary population study performed in eight French districts then, allowed assessing the frequency of self-referred screening (mammography performed out of program). RESULTS: The rate of participation in screening programs, in relation to the invited population, ranged from 21 to 48%, according to the district (36% in average). This low participation was probably related to the extent of self-referred screening. In fact, 19 to 40% of women, according to the district, had previously had a screening mammographic coverage: rate was around 68% in women aged 50 to 69 years. Positive findings with mammography ranged from 4.5 to 15.8% (10.1% in average), while intervention rates ranged from 0.7 to 1.6% and detection rates from 3.8 to 6.2%. The ratio between benign tumors and cancers ranged from 0.7 to 2.1 according to the district. In order to enlighten the judgement on French results, we propose a comparison with the international standards in force. CONCLUSION: The various experiences with breast cancer screening in France show that this screening is technically feasible on the basis of existing medical structures. However, some criteria are still below the expected values, especially if compared with international standards. This result is probably accounted for by the high rate self-referred screening before age 40 in France. In these conditions, the question is whether extending breast cancer screening programs in France is an appropriate course of action.

Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes.

We describe eight patients with slowly progressive speech production deficit combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and initially no other deficit in other language and non-language neuropsychological domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and frontal lobe cognitive slowing without generalised intellectual deterioration. Most disabled patients presented with an anterior opercular syndrome (Foix-Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI findings disclosed asymmetric (left > right) progressive cortical atrophy of the frontal lobes predominating in the posterior inferior frontal region, notably the operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism, prominent in the left posterior-inferior frontal gyrus and premotor cortex, extending bilaterally in the most advanced cases. Pathological study of two cases showed non-specific neuronal loss, gliosis, and spongiosis of superficial cortical layers, mainly confined to the frontal lobes, with no significant abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except severe neuronal loss in the substantia nigra in one case), and spinal cord. We propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based on its specific clinical presentation, and its metabolic and pathological correlates. SPA represents another clinical expression of focal cortical degeneration syndromes, that may overlap with other similar syndromes, specially primary progressive aphasia and the various frontal lobe dementias.