Somatosensory motor bodily representation cortical thinning in Tourette : effects of tic severity, age and gender

Introduction: Tourette syndrome (TS) implicates the disinhibition of the cortico-striatal-thalamic-cortical circuitry (CSTC). Previous studies used a volumetric approach to investigate this circuitry with inconsistent findings. Cortical thickness may represent a more reliable measure than volume due to the low variability in the cytoarchitectural structure of the grey matter. Methods: 66 magnetic resonance imaging scans were acquired from 34 TS (age range 10-25, mean 17.19±4.1) and 32 normal controls (NC) (age range 10-20, mean 16.33±3.56). Brain morphology was assessed using the fully automated Civet pipeline at the Montreal Neurological Institute. Results: We report (1) significant cortical thinning in the fronto-parietal and somatosensory-motor cortices in TS relative to NC (p<0.05); (2) TS boys showed thinner cortex relative to TS girls in the fronto-parietal cortical regions (p<0.05); (3) significant decrease in the fronto-parietal mean cortical thickness in TS with age relative to NC and in the pre-central cortex in TS boys relative to TS girls; (4) significant negative correlations between tic severity and the somatosensory-motor cortical thickness. Conclusions: TS revealed important thinning in brain regions particularly involved in the somatosensory/motor bodily representations which may play an important role in tics. Our findings are in agreement with Leckman et al. (1991) hypothesis stating that facial tics would be associated with dysfunction in an orofacial subset of the motor circuit, eye blinking with the occulo-motor circuit, whereas lack of inhibition to a dysfunction in the prefrontal cortex. Gender and age differences may reflect differential etiological factors, which have significant clinical relevance in TS and should be considered in developing and using diagnostic and therapeutic interventions.

Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis.

Mucocutaneous leishmaniasis is caused by infections with intracellular parasites of the Leishmania Viannia subgenus, including Leishmania guyanensis. The pathology develops after parasite dissemination to nasopharyngeal tissues, where destructive metastatic lesions form with chronic inflammation. Currently, the mechanisms involved in lesion development are poorly understood. Here we show that metastasizing parasites have a high Leishmania RNA virus-1 (LRV1) burden that is recognized by the host Toll-like receptor 3 (TLR3) to induce proinflammatory cytokines and chemokines. Paradoxically, these TLR3-mediated immune responses rendered mice more susceptible to infection, and the animals developed an increased footpad swelling and parasitemia. Thus, LRV1 in the metastasizing parasites subverted the host immune response to Leishmania and promoted parasite persistence.

A Novel Acute Retroviral Syndrome Severity Score Predicts the Key Surrogate Markers for HIV-1 Disease Progression.

OBJECTIVE: Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression. METHODS: We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined "Acute Retroviral Syndrome Severity Score" (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4+ cell count, and log viral setpoint (sVL) (i.e. VL measured ≥90 days after infection or treatment interruption). RESULTS: Mean ARSSS was 2.89. CD4+ cell count at baseline was negatively correlated with ARSSS (p = 0.03, n = 289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n = 290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4+cell count decline of 12/µl, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p = 0.029, n = 64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p = 0.28, n = 40). CONCLUSION: The ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.

Anxiety and severity of illicit substance use in adolescence: Evaluating the mediating role of perceived coping styles

The purpose of this study was to examine whether coping styles (Active coping, Internal coping and Withdrawal coping) mediated the relationships between anxiety and severity of illicit substance use among a sample of 110 Swiss adolescents ages 12-19 (M=16.3, SD=1.66). The current study tested two competing models of anxiety on severity of illicit substance use. In the first model, we tested the direct effect of trait anxiety (STAI-Y anxiety score) on severity of illicit substance use (ADAD drug use severity rating), while in the second models we examined the mediating role of coping styles in the link between trait anxiety and severity of illicit substance use. Path models indicated that the associations between trait anxiety and severity of illicit substance use are partially mediated by active and withdrawal coping styles. Limitations of the findings and implications for prevention of substance use in adolescence are discussed.

Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes.

BACKGROUND: Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. OBJECTIVES: The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. METHODS: Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. RESULTS: A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. CONCLUSIONS: FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

The pneumonia severity index: a decade after the initial derivation and validation

The prognosis of community-acquired pneumonia ranges from rapid resolution of symptoms and full recovery of functional status to the development of severe medical complications and death. The pneumonia severity index is a rigorously studied prediction rule for prognosis that objectively stratifies patients into quintiles of risk for short-term mortality on the basis of 20 demographic and clinical variables routinely available at presentation. The pneumonia severity index was derived and validated with data on >50,000 patients with community-acquired pneumonia by use of well-accepted methodological standards and is the only pneumonia decision aid that has been empirically shown to safely increase the proportion of patients given treatment in the outpatient setting. Because of its prognostic accuracy, methodological rigor, and effectiveness and safety as a decision aid, the pneumonia severity index has become the reference standard for risk stratification of community-acquired pneumonia

A tennis player with hand claudication.

The case of a professional tennis player presenting exercise-induced hand pain with late appearance of digital blanching is reported. A bilateral hypothenar hammer syndrome and stenosis of the common palmar digital arteries close to the head of the metacarpals where the racket handle exerts its maximal force was observed with arteriography. As the patient decided to stop tennis practice, the condition improved without any medication. Six months after stopping tennis he was symptom free. Three conclusions can be drawn from this case report: 1) arteries of both hands can be injured by intense tennis practice, 2) pain in the dominant hand during tennis practice can be due to arterial insufficiency even in the absence of digital blanching which is a sign of severity, 3) hypothenar hammer syndrome is the main cause but stenosis of the common palmar digital arteries can possibly contribute to the ischemic phenomenon. Early recognition is important to avoid ineffective treatment and permanent symptoms. Therefore, we recommend an arterial examination in tennis players suffering from exercise-induced hand pain even in the absence of digital blanching which can be only a late manifestation.

Defensive flexibility and its relation to symptom severity, depression, and anxiety.

Numerous studies have examined which individual defense mechanisms are related with mental health, and which are linked with psychopathology. However, the idea that a flexible use of defensive mechanisms is related to psychological wellbeing remained a clinical assumption, which this study sought to test empirically. A total of 62 (N = 62) outpatients participated in the study and were assessed with the Symptom Checklist-90R and the Social Adjustment Self-rated Scale. A subsample of 40 participants was further assessed using the Hamilton Depression (HAMD-21) and Anxiety scales (HAMA-21). The first therapy session of all participants was transcribed and rated using the Defense Mechanisms Ratings Scales (), and the Overall Defensive Functioning (ODF) score, which indicates the maturity of one's defensive functioning, was computed. An indicator of flexible use of defenses was also calculated based on the Gini Concentration C measure. Results showed that defensive flexibility, but not ODF, could predict anxiety scores. Symptom severity was predicted by both ODF and defensive flexibility, although in directions opposite to our predictions. Results suggest that defensive flexibility captures another aspect of an individual's functioning not assessed by the ODF, and that it is a promising new way of documenting defensive functioning.

Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome.

Body fluid biomarkers of central nervous system damage may help improve the prognostic and diagnostic accuracy in ischemic stroke. We studied 53 patients. Stroke severity and outcome was rated using the National Institutes of Health Stroke Scale and modified Rankin scale. Ferritin, S100B, and NfH were measured in cerebrospinal fluid (CSF) and serum. Infarct volume was calculated from T2W images. CSF S100B (median 1.00 ng/mL) and CSF ferritin (10.0 ng/mL) levels were elevated in patients with stroke compared with control subjects (0.62 ng/mL, P < .0001; 2.34 ng/mL, P < .0001). Serum S100B (0.09 ng/mL) was higher in patients with stroke compared with control subjects (0.01 ng/mL). CSF S100B levels were higher in patients with a cardioembolic stroke (2.88 ng/mL) than in those with small-vessel disease (0.89 ng/mL, P < .05). CSF S100B levels correlated with the National Institutes of Health Stroke Scale score on admission (R = 0.56, P < .01) and the stroke volume (R = 0.44, P = .01). CSF S100B and NfH-SMI35 levels correlated with outcome on the modified Rankin scale. CSF S100B levels were related to stroke severity and infarct volume and highest in cardioembolic stroke.

Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner.

BACKGROUND & AIMS: Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. METHODS: We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. RESULTS: The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P = .020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS: The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE.

Alterations in the local myocardial motion pattern in patients suffering from pressure overload due to aortic stenosis.

BACKGROUND: MR tissue tagging allows the noninvasive assessment of the locally and temporally resolved motion pattern of the left ventricle. Alterations in cardiac torsion and diastolic relaxation of the left ventricle were studied in patients with aortic stenosis and were compared with those of healthy control subjects and championship rowers with physiological volume-overload hypertrophy. METHODS AND RESULTS: Twelve aortic stenosis patients, 11 healthy control subjects with normal left ventricular function, and 11 world-championship rowers were investigated for systolic and diastolic heart wall motion on a basal and an apical level of the myocardium. Systolic torsion and untwisting during diastole were examined by use of a novel tagging technique (CSPAMM) that provides access to systolic and diastolic motion data. In the healthy heart, the left ventricle performs a systolic wringing motion, with a counterclockwise rotation at the apex and a clockwise rotation at the base. Apical untwisting precedes diastolic filling. In the athlete's heart, torsion and untwisting remain unchanged compared with those of the control subjects. In aortic stenosis patients, torsion is significantly increased and diastolic apical untwisting is prolonged compared with those of control subjects or athletes. CONCLUSIONS: Torsional behavior as observed in pressure- and volume-overloaded hearts is consistent with current theoretical findings. A delayed diastolic untwisting in the pressure-overloaded hearts of the patients may contribute to a tendency toward diastolic dysfunction.

Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. METHODS: We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. RESULTS: Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) -0.20 days, 95% CI -0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04). CONCLUSIONS: No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.

Partial cricotracheal resection for pediatric subglottic stenosis: a single institution's experience in 60 cases.

In our study, 60 infants and children, each with a severe subglottic stenosis (SGS), underwent partial cricotracheal resection (PCTR) with primary thyrotracheal anastomosis. According to the Myer-Cotton classification, two were grade II, 41 were grade III and 17 were grade IV stenoses. Of the 60 patients, 57 (95%) are presently decannulated, and one patient sustained a complete restenosis. Two patients with better than 80% subglottic airways still are waiting for decannulation: one because of bilateral cricoarytenoid joint fixation and the second because of temporary stenting of the subglottis with a Montgomery T-tube. The rate of decannulation is 97% (36 of 37 cases) in primary PCTRs, 100% (13 of 13 cases) in salvage PCTRs for failed laryngotracheal reconstructions (LTR) and 70% (7 of 10 cases) in extended PCTRs (i.e., PCTR associated with an additional open-airway procedure).