EPA guidance on assessment of negative symptoms in schizophrenia.

BACKGROUND: During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent. METHODS: In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice. RESULTS: Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings. CONCLUSIONS: The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

[Neurological complications attributable to lithium: An update]. / Complications neurologiques imputables au lithium : mise au point.

Lithium intoxication may induce neurological complications, initially characterised by a conscience alteration and an encephalopathy clinical picture with a risk of death or sever long-term consequences. With an occurrence sometimes atypical and possibly without initial hyperlitemia, the diagnosis delay of these complications might be important. Moreover, no specific guidelines focused on these complications are available. The aim of this article is to propose an update on diagnosis and treatment of neurological complications attributable to lithium, as encephalopathy.

Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study.

The fronto-striato-thalamic circuitry is a key network in patients with schizophrenia (SZPs). We use diffusion tensor imaging (DTI) to investigate the integrity of white matter (WM) pathways involved in this network in SZPs relative to healthy controls (HCs). We also evaluate the differential impact of chronic exposure to clozapine as well as other atypical and typical antipsychotics. 63 HCs and 41 SZPs were included. Of the SZPs, 16 were treated with clozapine (SZPsC), 17 with atypical antipsychotics (SZPsA), and 8 with typical antipsychotics (SZPsT). Three tracts were reconstructed in the left hemisphere using tractography: one fronto-subcortical tract, one prefronto-subcortical tract, and one prefronto-frontal tract. Diffusion parameters were individually extracted in each tract. SZPs exhibited lower integrity in both the fronto-subcortical and prefronto-subcortical tracts relative to HCs, and SZPsT showed altered integrity compared to SZPsC. There were no WM integrity differences in the prefronto-frontal tract between SZP groups or between SZPs and HCs. SZPs exhibit structural connectivity abnormalities in the prefronto-fronto-subcortical network that are specifically and differentially impacted by the type of antipsychotic treatment. Additional studies are needed to separate the contributions of clozapine-mediated neuroprotection, neurotoxicity related to typical antipsychotics, and the illness itself to observed differences.

Candidate gene association study for noise-induced hearing loss in two independent noise-exposed populations.

Millions of people are daily exposed to high levels of noise. Consequently, noise-induced hearing loss (NIHL) is one of the most important occupational health hazards worldwide. In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. Calculation of odds ratios revealed a significant association of rs588035 with NIHL in the Swedish high noise exposure level group. Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but further replication in independent sample sets is mandatory.

A new, easy, and rapid high-throughput detection method for the common GJB2 (CX26), 35delG mutation.

GJB2 (Gap Junction protein beta type 2; Connexin 26, CX26) is known for its contribution to nonsyndromic recessive deafness (NSRD). One particular mutation, 35delG, a deletion of one guanine from a stretch of six leading to a frame shift early in the gene, has a high prevalence in populations from European descent. 35delG testing therefore has become a standard test in genetic diagnostic laboratories. Most of the currently available methods for the detection of 35delG are relatively time consuming, and not suited for high-throughput diagnostic testing. Within this paper we present a real-time PCR genotyping assay based on melting curve analysis, requiring only a single preparation step before the actual analysis. The assay was optimized on a panel of 48 samples with known 35delG genotypes and subsequently tested using a large Belgian population (N = 460) with unknown 35delG status. For the latter set of samples, real-time PCR results were validated with SNAPShot, an assay used in our laboratory for diagnostic purposes. The real-time PCR genotyping method has proven to be highly reliable, rapid, cost-effective, and suitable for high-throughput screening. We believe that this genetic test for 35delG will find widespread applications in the DNA diagnostic field.

KCNQ4: a gene for age-related hearing impairment?

Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Zhigh and Zlow, a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p-values for two SNPs for Zhigh-SNP9 (NT_004511:g.11244177A > T) and SNP15 (NT_004511:g.11257005C > T; NP_004691:p.Ala259Ala), and one SNP for Zlow-SNP12 (NT_004511:g.11249550A > T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNPs, resulting in three LD-blocks. LD-block 1 contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A > G) to SNP18 (NT_004511:g.11257509G > A; NP_004691:p.Thr293Thr), and LD-block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNPs of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene.

Sclerosing osteomyelitis and Actinomyces naeslundii infection of surrounding tissues.

We present the case of a young man with chronic Actinomyces naeslundii infection in the lower leg who underwent a below-the-knee amputation after unsuccessful attempts at diagnosing and eradicating the infection. Actinomycetic organisms from environmental sources can engender a dense fibrotic tissue response without fistulae. Such a response led to a painful, sclerosing, nonsuppurative infection of the bone and surrounding tissues in our patient. This clinical picture, at least the bony and periosteal reaction, was compatible with Garrè's osteomyelitis.

Endoscopic obliteration of recurrent tracheoesophageal fistula.

We report a successful endoscopic obliteration of a large recurrent tracheoesophageal fistula (diameter 0.6 cm, length 2.0 cm) in a 12-year-old girl, using a combination of Histoacryl (n-butyl-z-cyanoacrylate) and Aethoxysclerol injected through a polyethylene catheter. The severe pulmonary infection, which rendered surgery potentially life threatening, disappeared after the endoscopic closure. Since the obliteration, now over 12 months ago, the girl is asymptomatic. Endoscopic obliteration is a worthwhile technique and should be considered as an alternative to surgery in patients presenting with a complicated recurrent tracheoesophageal fistula.

[Endoscopic closure of a recurrent tracheoesophageal fistula]. / Fermeture endoscopique d'une fistule trachéo-oesophagienne récidivante.

We report a successful endoscopic obliteration of a large recurrent tracheo-esophageal fistula (diameter 0.6 cm, length 2 cm) in a 12-year old girl, using a combination of N-butyl-2-cyanoacrylate followed by polidocanol injected through a polyethylene catheter. The severe pulmonary infection, that rendered surgery potentially life-threatening, resolved after endoscopic closure. The girl remained asymptomatic for 14 months after the first obliteration. Chronic coughing was the symptom of relapse. A follow-up endoscopy revealed that most of the N-butyl-2-cyanoacrylate had disappeared from the fistula, whose endoscopic appearance was unchanged. A second obliteration with the same products was performed. The girl has again been asymptomatic for 10 months. The endoscopic obliteration is a worth-while technique, to be considered as an alternative to surgery in patients presenting with a complicated recurrent tracheo-oesophageal fistula.

Mycobacterium fortuitum midpalmar space abscess: a case report.

A case report of a midpalmar abscess from Mycobacterium fortuitum is presented. It appeared 4 weeks after a penetrating nail injury to the palm and wrist and resolved with chemotherapeutic and surgical treatment.