Bacteremia and adrenal gland abscess due to Nocardia cyriacigeorgica: a case report and review.

BACKGROUND: Nocardia cyriacigeorgica is one of the most common Nocardia species found in human infections, recently reclassified. Even though Nocardia may affect all organs by hematogenous dissemination, bacteremia are uncommon. Among all possible dissemination sites, the involvement of the adrenal glands is particularly rare. CASE PRESENTATION: We report here a rare case of Nocardia disseminated infection with notably bacteremia and adrenal gland abscess, in a 77-years-old immunocompetent man. Adrenal gland abscess diagnosis was made by imaging (computerized tomography, magnetic resonance and positron emission tomography scan). A complete regression of all lesions including the left adrenal gland was obtained after 6 months of antibiotics. A review of literature was also performed. CONCLUSION: Nocardia bacteremia is a rare event but blood cultures may help to improve detection of Nocardia spp. in a non-invasive way. Adrenal abscess due to Nocardia spp. is very rare with only fourteen cases reported in the literature, but it is a true cause of adrenal masses. Our report suggests that clinician should be aware of this rare location and prioritize a non-invasive diagnosis strategy.

Physiological effects of a spit sock.

OBJECTIVES: Healthcare providers and law enforcement utilize spit socks to prevent exposure to communicable diseases transmitted by bodily fluid projection from agitated individuals. There are cases in which death is reported due to breathing being limited by a spit sock. There are no formally published studies on their use and safety. The aim of this study was to evaluate whether wearing a spit sock causes a clinically significant impact on breathing. METHODS: Subjects sat with the spit mask over their heads for 15 min and their vital signs and ventilatory parameters were recorded after 5 min, 10 min and 15 min. Data were compared to baseline using Student's t-test with 95% confidence intervals using SPSS. RESULTS: The median age of the 15 subjects was 28 years and 53% were male. There was no significant difference between baseline and wearing the spit sock for 5, 10 or 15 min for heart rate (p = 0.250, p = 0.181, p = 0.546), oxygen saturation (p = 0.334, p = 1.00, p = 0.173), end-tidal pCO2 (p = 0.135, p = 0.384, p = 0.187), and diastolic blood pressure (p = 0.485, p = 0.508, p = 0.915). The respiratory rate was not significantly different after 5 and 10 min (p = 0.898, p = 0.583), but decreased at 15 min (p = 0.048). The systolic blood pressure was lower after 5 and 10 min (p = 0.028, p = 0.045), but not significantly different at 15 min (p = 0.146). No subject indicated distress nor did the study need to be terminated due to pre-determined concerning vital signs or ventilatory parameters. CONCLUSIONS: In healthy subjects there were no clinically significant changes in the physiologic parameters of breathing while wearing a spit sock.

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

The assessment of auditory function in CSWS: lessons from long-term outcome.

In Landau-Kleffner syndrome (LKS), the prominent and often first symptom is auditory verbal agnosia, which may affect nonverbal sounds. It was early suggested that the subsequent decline of speech expression might result from defective auditory analysis of the patient's own speech. Indeed, despite normal hearing levels, the children behave as if they were deaf, and very rapidly speech expression deteriorates and leads to the receptive aphasia typical of LKS. The association of auditory agnosia more or less restricted to speech with severe language decay prompted numerous studies aimed at specifying the defect in auditory processing and its pathophysiology. Long-term follow-up studies have addressed the issue of the outcome of verbal auditory processing and the development of verbal working memory capacities following the deprivation of phonologic input during the critical period of language development. Based on a review of neurophysiologic and neuropsychological studies of auditory and phonologic disorders published these last 20 years, we discuss the association of verbal agnosia and speech production decay, and try to explain the phonologic working memory deficit in the late outcome of LKS within the Hickok and Poeppel dual-stream model of speech processing.

Is there an alternative cerebral network associated with enhanced phonological processing in deaf speech-users? An exceptional case.

Most people born deaf and exposed to oral language show scant evidence of sensitivity to the phonology of speech when processing written language. In this respect they differ from hearing people. However, occasionally, a prelingually deaf person can achieve good processing of written language in terms of phonological sensitivity and awareness, and in this respect appears exceptional. We report the pattern of event-related fMRI activation in such a deaf reader while performing a rhyme-judgment on written words with similar spelling endings that do not provide rhyme clues. The left inferior frontal gyrus pars opercularis and the left inferior parietal lobe showed greater activation for this task than for a letter-string identity matching task. This participant was special in this regard, showing significantly greater activation in these regions than a group of hearing participants with a similar level of phonological and reading skill. In addition, SR showed activation in the left mid-fusiform gyrus; a region which did not show task-specific activation in the other respondents. The pattern of activation in this exceptional deaf reader was also unique compared with three deaf readers who showed limited phonological processing. We discuss the possibility that this pattern of activation may be critical in relation to phonological decoding of the written word in good deaf readers whose phonological reading skills are indistinguishable from those of hearing readers.

Landau-Kleffner syndrome is not an eponymic badge of ignorance.

In a 1992 editorial article, Landau expressed the hope of collective agreement in the medical community about Landau-Kleffner syndrome (LKS) in terms of diagnosis criteria, etiology, pathophysiology and rational therapy. Since then, neurophysiological and neuroimaging studies have led to the view that LKS is an acquired aphasia, secondary to an epileptic disturbance affecting a cortical area involved in verbal processing. This fits with the hypothesis of a "functional ablation" caused by epileptic activity. Under these criteria, epileptic aphasia becomes a subgroup of the continuous spike-waves syndrome in which epileptic discharges originate from the temporal cortex. Genetic predisposition for KLS could be related to hyperexcitability and synchronization of interneurons within the perisylvian cortices, which generate the spike-waves. Activation of these waves during NREM sleep, following thalamo-cortical uncoupling, might then alter the blood brain barrier and provoke an autoimmune reaction. Interneuron hyperactivity might in turn have an antiepileptic protective effect, associated with the inhibition of a specific function, and spike-waves activity over the long term might eventuate in focal atrophy. This morphological defect might explain the poor verbal outcome in some cases of LKS. From this study we recommend a multicenter control study of good design and methodology be carried out to compare the efficacies of early versus delayed (3 months) corticosteroid treatment in patients with typical LKS that is being treated by clobazam (or diazepam) monotherapy.

Reliability of individual functional MRI brain mapping of language.

The use of individual brain mapping for a single case study implicitly assumes that the pattern of activation obtained in a single session represents the subject's functional neuroanatomy. It is therefore essential to estimate the potential variability of brain activation in individuals. To this purpose, the authors compared the pattern of activation determined by statistical parametric mapping (SPM 99) in 9 subjects who repeated 3 verbal tasks in 3 separate sessions. In each subject for each task, the authors examined the intersession variability of the volume of activation in a set of regions classically implicated in language processing. Their results show that reproducibility of functional MRI brain mapping for language within subject varies as a function of the activation task and the region of interest for language.

Unsupervised learning and mapping of active brain functional MRI signals based on hidden semi-Markov event sequence models.

In this paper, a novel functional magnetic resonance imaging (fMRI) brain mapping method is presented within the statistical modeling framework of hidden semi-Markov event sequence models (HSMESMs). Neural activation detection is formulated at the voxel level in terms of time coupling between the sequence of hemodynamic response onsets (HROs) observed in the fMRI signal, and an HSMESM of the hidden sequence of task-induced neural activations. The sequence of HRO events is derived from a continuous wavelet transform (CWT) of the fMRI signal. The brain activation HSMESM is built from the timing information of the input stimulation protocol. The rich mathematical framework of HSMESMs makes these models an effective and versatile approach for fMRI data analysis. Solving for the HSMESM Evaluation and Learning problems enables the model to automatically detect neural activation embedded in a given set of fMRI signals, without requiring any template basis function or prior shape assumption for the fMRI response. Solving for the HSMESM Decoding problem allows to enrich brain mapping with activation lag mapping, activation mode visualizing, and hemodynamic response function analysis. Activation detection results obtained on synthetic and real epoch-related fMRI data demonstrate the superiority of the HSMESM mapping method with respect to a real application case of the statistical parametric mapping (SPM) approach. In addition, the HSMESM mapping method appears clearly insensitive to timing variations of the hemodynamic response, and exhibits low sensitivity to fluctuations of its shape.

Hidden Markov event sequence models: toward unsupervised functional MRI brain mapping.

RATIONALE AND OBJECTIVES: Most methods used in functional MRI (fMRI) brain mapping require restrictive assumptions about the shape and timing of the fMRI signal in activated voxels. Consequently, fMRI data may be partially and misleadingly characterized, leading to suboptimal or invalid inference. To limit these assumptions and to capture the broad range of possible activation patterns, a novel statistical fMRI brain mapping method is proposed. It relies on hidden semi-Markov event sequence models (HSMESMs), a special class of hidden Markov models (HMMs) dedicated to the modeling and analysis of event-based random processes. MATERIALS AND METHODS: Activation detection is formulated in terms of time coupling between (1) the observed sequence of hemodynamic response onset (HRO) events detected in the voxel's fMRI signal and (2) the "hidden" sequence of task-induced neural activation onset (NAO) events underlying the HROs. Both event sequences are modeled within a single HSMESM. The resulting brain activation model is trained to automatically detect neural activity embedded in the input fMRI data set under analysis. The data sets considered in this article are threefold: synthetic epoch-related, real epoch-related (auditory lexical processing task), and real event-related (oddball detection task) fMRI data sets. RESULTS: Synthetic data: Activation detection results demonstrate the superiority of the HSMESM mapping method with respect to a standard implementation of the statistical parametric mapping (SPM) approach. They are also very close, sometimes equivalent, to those obtained with an "ideal" implementation of SPM in which the activation patterns synthesized are reused for analysis. The HSMESM method appears clearly insensitive to timing variations of the hemodynamic response and exhibits low sensitivity to fluctuations of its shape (unsustained activation during task). Real epoch-related data: HSMESM activation detection results compete with those obtained with SPM, without requiring any prior definition of the expected activation patterns thanks to the unsupervised character of the HSMESM mapping approach. Along with activation maps, the method offers a wide range of additional fMRI analysis functionalities, including activation lag mapping, activation mode visualization, and hemodynamic response function analysis. Real event-related data: Activation detection results confirm and validate the overall strategy that consists in focusing the analysis on the transients, time-localized events that are the HROs. CONCLUSION: All the experiments performed on synthetic and real fMRI data demonstrate the relevance of HSMESMs in fMRI brain mapping. In particular, the statistical character of these models, along with their learning and generalizing abilities are of particular interest when dealing with strong variabilities of the active fMRI signal across time, space, experiments, and subjects.

Visemic processing in audiovisual discrimination of natural speech: a simultaneous fMRI-EEG study.

In a noisy environment, visual perception of articulatory movements improves natural speech intelligibility. Parallel to phonemic processing based on auditory signal, visemic processing constitutes a counterpart based on "visemes", the distinctive visual units of speech. Aiming at investigating the neural substrates of visemic processing in a disturbed environment, we carried out a simultaneous fMRI-EEG experiment based on discriminating syllabic minimal pairs involving three phonological contrasts, each bearing on a single phonetic feature characterised by different degrees of visual distinctiveness. The contrasts involved either labialisation of the vowels, or place of articulation or voicing of the consonants. Audiovisual consonant-vowel syllable pairs were presented either with a static facial configuration or with a dynamic display of articulatory movements related to speech production. In the sound-disturbed MRI environment, the significant improvement of syllabic discrimination achieved in the dynamic audiovisual modality, compared to the static audiovisual modality was associated with activation of the occipito-temporal cortex (MT+V5) bilaterally, and of the left premotor cortex. While the former was activated in response to facial movements independently of their relation to speech, the latter was specifically activated by phonological discrimination. During fMRI, significant evoked potential responses to syllabic discrimination were recorded around 150 and 250 ms following the onset of the second stimulus of the pairs, whose amplitude was greater in the dynamic compared to the static audiovisual modality. Our results provide arguments for the involvement of the speech motor cortex in phonological discrimination, and suggest a multimodal representation of speech units.

What Physiological Changes and Cerebral Traces Tell Us about Adhesion to Fiction During Theater-Watching?

Live theater is typically designed to alter the state of mind of the audience. Indeed, the perceptual inputs issuing from a live theatrical performance are intended to represent something else, and the actions, emphasized by the writing and staging, are the key prompting the adhesion of viewers to fiction, i.e., their belief that it is real. This phenomenon raises the issue of the cognitive processes governing access to a fictional reality during live theater and of their cerebral underpinnings. To get insight into the physiological substrates of adhesion we recreated the peculiar context of watching live drama in a functional magnetic resonance imaging (fMRI) experiment, with simultaneous recording of heart activity. The instants of adhesion were defined as the co-occurrence of theatrical events determined a priori by the stage director and the spectators' offline reports of moments when fiction acted as reality. These data served to specify, for each spectator, individual fMRI time-series, used in a random-effect group analysis to define the pattern of brain response to theatrical events. The changes in this pattern related to subjects' adhesion to fiction, were investigated using a region of interest analysis. The results showed that adhesion to theatrical events correlated with increased activity in the left BA47 and posterior superior temporal sulcus, together with a decrease in dynamic heart rate variability, leading us to discuss the hypothesis of subtle changes in the subjects' state of awareness, enabling them to mentally dissociate physical and mental (drama-viewing) experiences, to account for the phenomenon of adhesion to dramatic fiction.

Reading disabilities in SLI and dyslexia result from distinct phonological impairments.

Children with specific language impairment (SLI) who show impaired phonological processing are at risk of developing reading disabilities, which raises the question of phonological impairment commonality between developmental dyslexia (DD) and SLI. In order to distinguish the failing phonological processes in SLI and DD, we investigated the different steps involved in speech processing going from perceptual discrimination through various aspects of phonological memory. Our results show that whereas the memory for sequence is likewise impaired in either disorder, children with SLI have to face additional impairment in phonological discrimination and short-term memory, which may account for even poorer phonological awareness than dyslexics'.

Phonological processing in relation to reading: an fMRI study in deaf readers.

Without special education, early deprivation of auditory speech input, hinders the development of phonological representations and may alter the neural mechanisms of reading. By using fMRI during lexical and rhyming decision tasks, we compared in hearing and pre-lingually deaf subjects the neural activity in functional regions of interest (ROIs) engaged in reading. The results show in deaf readers significantly higher activation in the ROIs relevant to the grapho-phonological route, but also in the posterior medial frontal cortex (pMFC) and the right inferior frontal gyrus (IFG). These adjustments may be interpreted within the dual route model of reading as an alternative strategy, which gives priority to rule-based letter-to-sound conversion. Activation in the right IFG would account for compensation mechanisms based on phonological recoding and inner speech while activation in the posterior medial frontal cortex (pMFC) may relate to the cognitive effort called for by the alternative strategy. Our data suggest that the neural mechanisms of reading are shaped by the auditory experience of speech.

Neuropsychological findings in Rolandic epilepsy and Landau-Kleffner syndrome.

In an attempt to correlate neuropsychological deficits and various neurophysiological aspects of focal epileptic activity in benign childhood epilepsy, we have reviewed the findings of a longitudinal group study of benign childhood epilepsy with centrotemporal spikes (BCECTS) and several case studies of continuous spike-waves during slow sleep syndrome (CSWS). We first distinguish the temporary neuropsychological impairments often observed in the natural history of BCECTS from the more long-lasting and more specific neuropsychological deficits associated with CSWS, of which the Landau-Kleffner syndrome (LKS) is the most studied clinical form. A series of metabolic findings from (18)FDG-PET studies in BCECTS and CSWS children have shown that specific cognitive impairment is related to increased glucose uptake in cortical areas restricted to the associative cortex coincident with the focus of spike-wave discharges. From recent functional neuroimaging data of three patients recovered from LKS, we address the issue of the pathophysiology of cognitive impairment persisting after complete recovery of epilepsy. Finally, we discuss the reliability of the study of mismatch negativity to address the issue of the early effect of interictal discharges in typical and atypical BCECTS on the auditory cortex and the development of speech processing essential to verbal learning.

Analysis of polymorphism in the protease and reverse transcriptase genes of HIV type 1 CRF02-AG subtypes from drug-naive patients from Saint-Etienne, France.

SUMMARY: : The proportion of non-B HIV-1 variants is increasing in Western Europe. The impact of the high polymorphism in the protease and reverse transcriptase genes, as recently described for CRF02-AG isolates of African origin, on antiretroviral resistance is still disputed. We first examined the polymorphism of these genes in CRF02-AG strains recovered from drug-naive patients followed at the University Hospital of Saint-Etienne in France, most of these of French origin and harboring a clonal strain as elicited by phylogenic analysis. The first plasma sample detected positive from 31 CRF02-AG and 23 B strains was used to compare sequences with their respective subtype consensus strain. The overall number of mutations was dramatically higher for CRF02-AG strains than for B strains in both protease and reverse transcriptase genes (P < 0.0001 and 0.009, respectively). In addition, no statistically significant difference in the number of therapeutic failures, mean CD4 cell count, and viral load was observed between 22 and 45 patients infected with CRF02-AG or B strains, respectively, during a mean treatment period of 25.5 months. Even if no striking antiretroviral failure linked to this polymorphism was observed during short-term follow-up, its impact on long-term therapy will have to be extensively evaluated in patients infected by non-B HIV-1 variants.

Neural responses associated with positive and negative emotion processing in patients with left versus right temporal lobe epilepsy.

Studies on emotion processing in patients with temporal lobe epilepsy have dealt mainly with the processing of negative emotions. To further understand the neural basis of emotional disorders in temporal lobe epilepsy, we studied patterns of brain activation induced by implicit processing of negative and positive emotions perceived through facial expressions and emotionally salient stimuli in candidates for surgical treatment of intractable epilepsy. Using functional MRI, we compared, in patients with mesial temporal lobe epilepsy and healthy subjects, the patterns of brain activation elicited by the implicit processing of fearful, sad, and happy faces and pleasant and unpleasant scenes. The results revealed different patterns of activation in patients with left and right mesial temporal lobe epilepsy, compared with healthy subjects, suggesting that the left and right mesial temporal regions are involved differently in emotion processing, which could be related to different contributions in emotional arousal.

SRPX2 mutations in disorders of language cortex and cognition.

The rolandic and sylvian fissures divide the human cerebral hemispheres and the adjacent areas participate in speech processing. The relationship of rolandic (sylvian) seizure disorders with speech and cognitive impairments is well known, albeit poorly understood. We have identified the Xq22 gene SRPX2 as being responsible for rolandic seizures (RSs) associated with oral and speech dyspraxia and mental retardation (MR). SRPX2 is a secreted sushi-repeat containing protein expressed in neurons of the human adult brain, including the rolandic area. The disease-causing mutation (N327S) resulted in gain-of-glycosylation of the secreted mutant protein. A second mutation (Y72S) was identified within the first sushi domain of SRPX2 in a male with RSs and bilateral perisylvian polymicrogyria and his female relatives with mild MR or unaffected carrier status. In cultured cells, both mutations were associated with altered patterns of intracellular processing, suggesting protein misfolding. In the murine brain, Srpx2 protein expression appeared in neurons at birth. The involvement of SRPX2 in these disorders suggests an important role for SRPX2 in the perisylvian region critical for language and cognitive development.

Phonological short-term memory networks following recovery from Landau and Kleffner syndrome.

Landau-Kleffner syndrome (LKS) is a rare acquired aphasia occurring in otherwise healthy children, together with spike-wave discharges predominating over superior temporal regions and activated by sleep. Although the outcome of language abilities is variable, a residual impairment in verbal short-term memory (STM) is frequent. This STM deficit might be related to the persistent dysfunction of those temporal lobe regions where epileptic discharges were observed during the active phase of the disorder. We tested this hypothesis by measuring brain activation during immediate serial recall of lists of 4 words, compared to single word repetition, using H(2) (15)O positron emission tomography (PET), in 3 LKS patients after recovery and in 14 healthy controls. The patients (TG, JPH, and DC) had shown abnormally increased or decreased glucose metabolism in left or right superior temporal gyrus (STG) at different stages during the active phase of their disease. At the time of this study, the patients were 6-10 years from the active phase of LKS. Results showed that Patients JPH and DC had impaired performance in the STM condition, whereas TG showed near normal performance. PET data showed that JPH and DC activated significantly less than controls left and right posterior STG. TG, having near normal STM performance, showed increased activity in the posterior part of the right STG. These data suggest that impaired verbal STM at late outcome of LKS might indeed be related to a persistent decrease of activity in those posterior superior temporal gyri that were involved in the epileptic focus during the active phase.