An episode mimicking a versive seizure in acute bilateral pontine stroke.

Pontine ischemia usually results in focal deficits such as hemiparesis, facial palsy, dysarthria, disorders of eye movements or vertigo. Although rarely described, involuntary abnormal movements and "convulsions" due to pontine lesions can also occur. Here we describe a 67-year-old woman with hypertension who presented with a tonic movement mimicking a versive seizure in the acute phase of bilateral pontine ischemia. Post-stroke movement disorders are well known. They are usually associated with supratentorial lesions and rarely occur in the acute phase, but "seizure-like" episodes can be seen in pontine ischemia. Awareness of this rare phenomenon is useful for the management of acute stroke patients.

Acute painful diabetic neuropathy: an uncommon, remittent type of acute distal small fibre neuropathy.

INTRODUCTION: Acute painful diabetic neuropathy (APDN) is a distinctive diabetic polyneuropathy and consists of two subtypes: treatment-induced neuropathy (TIN) and diabetic neuropathic cachexia (DNC). The characteristics of APDN are (1.) the small-fibre involvement, (2.) occurrence paradoxically after short-term achievement of good glycaemia control, (3.) intense pain sensation and (4.) eventual recovery. In the face of current recommendations to achieve quickly glycaemic targets, it appears necessary to recognise and understand this neuropathy. METHODS AND RESULTS: Over 2009 to 2012, we reported four cases of APDN. Four patients (three males and one female) were identified and had a mean age at onset of TIN of 47.7 years (±6.99 years). Mean baseline HbA1c was 14.2% (±1.42) and 7.0% (±3.60) after treatment. Mean estimated time to correct HbA1c was 4.5 months (±3.82 months). Three patients presented with a mean time to symptom resolution of 12.7 months (±1.15 months). One patient had an initial normal electroneuromyogram (ENMG) despite the presence of neuropathic symptoms, and a second abnormal ENMG showing axonal and myelin neuropathy. One patient had a peroneal nerve biopsy showing loss of large myelinated fibres as well as unmyelinated fibres, and signs of microangiopathy. CONCLUSIONS: According to the current recommendations of promptly achieving glycaemic targets, it appears necessary to recognise and understand this neuropathy. Based on our observations and data from the literature we propose an algorithmic approach for differential diagnosis and therapeutic management of APDN patients.

Patterns of oxygen consumption during establishment of cephalocaudal polarity in the early chick embryo.

Oxygen uptake was studied during the establishment of cephalocaudal polarity in the very early chick embryo, i.e., 10 hr before (stage VI) and at laying (stage X). Oxygen fluxes in minute regions of the intact blastoderms were measured in vitro by scanning microspectrophotometry in the presence or absence of glucose. The oxygen consumption of the whole blastoderm remained constant (6 nmol O2 X hr-1) throughout the period studied, although the number of cells increased more than twofold. The regional oxygen fluxes varied from 0.41 to 1.13 nmol O2 X hr-1 X mm-2 at stage VI and from 0.42 to 0.70 nmol O2 X hr-1 X mm-2 at stage X. At stage VI, the oxygen flux in the center of the blastoderm was significantly higher than that in its periphery. This pattern remained evident when the values were corrected for cell number or for cytoplasmic volume. At stage X, there was a tendency for the oxygen fluxes to decrease from the posterior to the anterior regions of the area pellucida. Thus the pattern of oxidative metabolism in the late uterine embryos seems to change from radial to bilateral. This change of symmetry probably reflects the process of formation of the embryonic axis. In addition, the fact that the oxygen uptake was similar in the presence or absence of glucose suggests that early chick embryos metabolize essentially intracellular stores.

Pseudohypoaldosteronisms, report on a 10-patient series.

BACKGROUND: Type 1 pseudohypoaldosteronism (PHA1) is a salt-wasting syndrome caused by mineralocorticoid resistance. Autosomal recessive and dominant hereditary forms are caused by Epithelial Na Channel and Mineralocorticoid Receptor mutation respectively, while secondary PHA1 is usually associated with urological problems. METHODS: Ten patients were studied in four French pediatric units in order to characterize PHA1 spectrum in infants. Patients were selected by chart review. Genetic, clinical and biochemistry data were collected and analyzed. RESULTS: Autosomal recessive PHA1 (n = 3) was diagnosed at 6 and 7 days of life in three patients presenting with severe hyperkalaemia and weight loss. After 8 months, 3 and 5 years on follow-up, neurological development and longitudinal growth was normal with high sodium supplementation. Autosomal dominant PHA1 (n = 4) was revealed at 15, 19, 22 and 30 days of life because of failure to thrive. At 8 months, 3 and 21 years of age, longitudinal growth was normal in three patients who were given salt supplementation; no significant catch-up growth was obtained in the last patient at 20 months of age. Secondary PHA1 (n = 3) was diagnosed at 11, 26 days and 5 months of life concomitantly with acute pyelonephritis in three children with either renal hypoplasia, urinary duplication or bilateral megaureter. The outcome was favourable and salt supplementation was discontinued after 3, 11 and 13 months. CONCLUSIONS: PHA1 should be suspected in case of severe hyperkalemia and weight loss in infants and need careful management. Pathogenesis of secondary PHA1 is still challenging and further studies are mandatory to highlight the link between infection, developing urinary tract and pseudohypoaldosteronism.

La lithiase rénale: un marqueur du risque cardiovasculaire [Kidney stone as a cardiovascular risk marker].

Si le passage d'un calcul rénal est souvent considéré comme un événement médical mineur, quoique très douloureux, de plus en plus d'études indiquent qu'il doit être pris au sérieux puisqu'il peut indiquer un risque cardiovasculaire augmenté. Nous revoyons ici les études qui associent risque cardiovasculaire et calcul rénal et les liens physiopathologiques qui les unissent. Nous montrons que la lithiase est un événement intervenant tôt dans la vie d'un individu à risque de développer des complications cardiovasculaires. Ainsi, la lithiase ne doit pas être banalisée, mais doit être considérée comme une première alerte devant inciter le médecin traitant à recenser précocement les facteurs de risque cardiovasculaires et à mettre en place une stratégie de prévention. Cette approche pourrait permettre de diminuer l'incidence d'événements cardiovasculaires chez les patients formeurs de lithiases. Most of the time, kidney stones are considered as minor, but painful events. However, several studies have recently shown an association between kidney stone and an increased cardio-vascular risk. We review here these studies and explore the underlying pathophysiological hypotheses. At the end, we propose that lithiasis should be considered as a red flag intervening early during life-time and allowing a check of cardiovascular risk factors and early preventive intervention. Such approach may be successful in reducing the incidence of cardio-vascular events in stone formers.

Autofluorescence Findings Of A Novel Maculopathy In Patient With Spinocerebellar Ataxia Type 1 And Of A Cone - Rod Type Retinal Dysfunction In Three Generation Family With Spinocerebellar Ataxia Type 7

Purpose: To report a novel maculopathy in a patient with SCA1. To describe autofluorescence findings in family with SCA7 and associated cone-rod retinal dysfunction.Methods: 4 affected patients from two families were assessed to investigate a progressive loss of visual acuity (VA). Examinations included fundus photography, autofluorescence (AF) fundus fluorescein angiogragraphy (FFA) and optical coherence tomography. Electroretinogram (full-field) was performed in 2 affected patients. All patients had color vision testing using Ishihara pseudoisochromatic plates. Molecular analysis was performed in family 2.Results: The patient with known diagnosis of SCA1 had a visual acuity of 20/200 bilaterally and dyschromatopsia. He had saccadic pursuit. Fundus examination showed mild retinal pigment epithelium (RPE) changes at the macula. OCT showed bilateral macular serous detachment, which was not obvious at the FFA and explained his VA. AF imaging showed a central hyperfluorescence. The 45 year old proband from family 2 had a visual acuity of 200/20 and dyschromatopsia. ERG testing showed cone type dysfunction of photoreceptors. Her daughter affected at a younger age had the same ERGs findings. Fundus examination showed mild RPE changes in proband, normal findings in her daughter. AF imaging of both patients showed a ring of high density AF around the fovea. The ring was also obvious on near infrared AF. Later onset of gait imbalance led to the diagnosis of SCA7Conclusions: Within the group of spinocerebellar ataxias, only the type 7 is associated with retinal dysfunction. We present the first report of maculopathy associated with SCA1 causing severe vision loss. The ring of high density AF in SCA7 confirmed an early retinal photoreceptor dysfunction in patient with normal fundus.

Cognitive and emotional effects of carotid stenosis.

PRINCIPLES: Patients with carotid artery stenosis (CAS) are at risk of ipsilateral stroke and chronic compromise of cerebral blood flow. It is under debate whether the hypo-perfusion or embolism in CAS is directly related to cognitive impairment. Alternatively, CAS may be a marker for underlying risk factors, which themselves influence cognition. We aimed to determine cognitive performance level and the emotional state of patients with CAS. We hypo-thesised that patients with high grade stenosis, bilateral stenosis, symptomatic patients and/or those with relevant risk factors would suffer impairment of their cognitive performance and emotional state. METHODS: A total of 68 patients with CAS of ≥70% were included in a prospective exploratory study design. All patients underwent structured assessment of executive functions, language, verbal and visual memory, motor speed, anxiety and depression. RESULTS: Significantly more patients with CAS showed cognitive impairments (executive functions, word production, verbal and visual memory, motor speed) and anxiety than expected in a normative sample. Bilateral and symptomatic stenosis was associated with slower processing speed. Cognitive performance and anxiety level were not influenced by the side and the degree of stenosis or the presence of collaterals. Factors associated with less co-gnitive impairment included higher education level, female gender, ambidexterity and treated hypercholesterolemia. CONCLUSIONS: Cognitive impairment and increased level of anxiety are frequent in patients with carotid stenosis. The lack of a correlation between cognitive functioning and degree of stenosis or the presence of collaterals, challenges the view that CAS per se leads to cognitive impairment.

Sub-cortical and brainstem sites associated with chemo-stimulated increases in ventilation in humans.

We investigated the neural basis for spontaneous chemo-stimulated increases in ventilation in awake, healthy humans. Blood oxygen level dependent (BOLD) functional MRI was performed in nine healthy subjects using T2 weighted echo planar imaging. Brain volumes (52 transverse slices, cortex to high spinal cord) were acquired every 3.9 s. The 30 min paradigm consisted of six, 5-min cycles, each cycle comprising 45 s of hypoxic-isocapnia, 45 s of isooxic-hypercapnia and 45 s of hypoxic-hypercapnia, with 55 s of non-stimulatory hyperoxic-isocapnia (control) separating each stimulus period. Ventilation was significantly (p<0.001) increased during hypoxic-isocapnia, isooxic-hypercapnia and hypoxic-hypercapnia (17.0, 13.8, 24.9 L/min respectively) vs. control (8.4 L/min) and was associated with significant (p<0.05, corrected for multiple comparisons) signal increases within a bilateral network that included the basal ganglia, thalamus, red nucleus, cerebellum, parietal cortex, cingulate and superior mid pons. The neuroanatomical structures identified provide evidence for the spontaneous control of breathing to be mediated by higher brain centres, as well as respiratory nuclei in the brainstem.

16q24.1 microdeletion in a premature newborn: Usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn.

OBJECTIVE:: Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. DESIGN:: Descriptive case report. SETTING:: Genetic department and neonatal intensive care unit of a tertiary care children's hospital. INTERVENTIONS:: None. PATIENT:: We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. MEASUREMENTS AND MAIN RESULTS:: An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. CONCLUSIONS:: Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

Plastic brain mechanisms for attaining auditory temporal order judgment proficiency.

Accurate perception of the order of occurrence of sensory information is critical for the building up of coherent representations of the external world from ongoing flows of sensory inputs. While some psychophysical evidence reports that performance on temporal perception can improve, the underlying neural mechanisms remain unresolved. Using electrical neuroimaging analyses of auditory evoked potentials (AEPs), we identified the brain dynamics and mechanism supporting improvements in auditory temporal order judgment (TOJ) during the course of the first vs. latter half of the experiment. Training-induced changes in brain activity were first evident 43-76 ms post stimulus onset and followed from topographic, rather than pure strength, AEP modulations. Improvements in auditory TOJ accuracy thus followed from changes in the configuration of the underlying brain networks during the initial stages of sensory processing. Source estimations revealed an increase in the lateralization of initially bilateral posterior sylvian region (PSR) responses at the beginning of the experiment to left-hemisphere dominance at its end. Further supporting the critical role of left and right PSR in auditory TOJ proficiency, as the experiment progressed, responses in the left and right PSR went from being correlated to un-correlated. These collective findings provide insights on the neurophysiologic mechanism and plasticity of temporal processing of sounds and are consistent with models based on spike timing dependent plasticity.

Contracts, Reference Points, and Competition - Behavioral Effects of the Fundamental Transformation

In this paper we study the role of incomplete ex ante contracts for ex post trade. Previous experimental evidence indicates that a contract provides a reference point for entitlements when the terms are negotiated in a competitive market. We show that this finding no longer holds when the terms are determined in a non-competitive way. Our results imply that the presence of a "fundamental transformation" (i.e., the transition from a competitive market to a bilateral relationship) is important for a contract to become a reference point. To the best of our knowledge this behavioral aspect of the fundamental transformation has not been shown before.

Endoscopic and surgical treatment of vesico-ureteral reflux in children. Comparative long-term follow-up.

PRINCIPLES: This retrospective study analyzes the long-term results of endoscopic and surgical treatment of vesico-ureteral reflux in children. METHODS: A cohort of 130 patients, 67 girls and 63 boys with a mean age of 30 months were treated either by endoscopic subureteral collagen injection (SCIN) in 92 and by Cohen reimplantation surgery in 123 refluxing ureteral units. Mean follow-up was 4.2 years varying from 1 to 8.7 years. Reflux recurrence, urinary tract infection (UTI) and renal function were evaluated. RESULTS: After SCIN reflux was absent in 64% at 6 months. 20% of the initially 92 refluxing ureters were injected twice. After one or two injections reflux was absent in 71%. In 21% recurrent reflux was of grade I or II, not requiring further treatment. UTI was observed in 27%. After Cohen ureteral reimplantation reflux was absent in 96% at 6 months. UTI was observed in 23%. Renal function at diagnosis and follow-up was compared in children with bilateral grade III reflux only. In patients treated with SCIN it was normal in 77% preoperatively and in 90% at follow-up. In patients treated by open surgery it was normal in 47% preoperatively and in 76% at follow-up. CONCLUSION: For high-grade vesico-ureteral reflux re-implantation surgery remains the gold standard. SCIN is indicated for low and medium grade reflux. Recurrent bacteriuria was observed more often after SCIN and pyelonephritis more often after open surgery. The renal function seems to be preserved with both techniques.

A 3-step therapeutic strategy for severe alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of lipoproteinaceous material in the terminal airways. Whole lung lavage (WLL) remains the gold standard treatment but may be particularly challenging in cases of severe hypoxemia. We present a 3-step strategy that was used in a patient with PAP-associated refractory hypoxemia and that combined venovenous extracorporeal membrane oxygenation (vvECMO), double-lumen orotracheal intubation, and bilateral multisegmental sequential lavage (MSL). The procedure was well tolerated and permitted weaning from the ventilator.

Spectrum of digoxin-induced ocular toxicity: a case report and literature review.

BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION: Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.