The low dopamine hypothesis: A plausible mechanism underpinning residual urine, overactive bladder and nocturia (RON) syndrome in older patients.

INTRODUCTION: Aging is associated with a combination of several lower urinary tract (LUT) signs and symptoms, including residual urine, overactive bladder and nocturia. One of the mechanisms of this LUT dysfunction that has not been discussed in dept so far is the role of dopamine (DA). METHODS: In this narrative review, we explore the dopaminergic hypothesis in the development of this combination of LUT signs and symptoms in older adults. RESULTS: DA is one of the neurotransmitters whose regulation and production is disrupted in aging. In synucleinopathies, altered DAergic activity is associated with the occurrence of LUTS and sleep disorders. Projections of DAergic neurons are involved in the regulation of sleep, diuresis, and bladder activity. The low dopamine hypothesis could explain the genesis of a set of LUT signs and symptoms commonly seen in this population, including elevated residual urine, Overactive bladder syndrome and Nocturia (discussed as the RON syndrome). This presentation is however also common in older patients without synucleinopathies or neurological disorders and therefore we hypothesise that altered DAergic activity because of pathological aging, and selective destruction of DAergic neurons, could underpin the presentation of this triad of LUT dysfunction in the older population. CONCLUSION: The concept of RON syndrome helps to better understand this common phenotypic presentation in clinical practice, and therefore serves as a useful platform to diagnose and treat LUTS in older adults. Besides recognizing the synucleinopathy "red flag" symptoms, this set of multi-causal LUT signs and symptoms highlights the inevitable need for combination therapy, a challenge in older people with their comorbidities and concomitant medications.

[Gender variance or gender dysphoria and autism spectrum disorder in children and adolescents]. / Gendervariatie en -dysforie bij autisme-spectrumstoornissen bij kinderen en adolescenten.

BACKGROUND: Clinical experience suggests that gender variance (GV) and/or gender dysphoria (GD) and autism spectrum disorder (ASD) characteristics co-occur more frequently than expected. AIM: This literature review examines the available publications focusing on the co-occurrence of GD/GV and ASD in children and adolescents. METHOD: PubMed and Embase were systematically searched for relevant publications with search terms related to 'autism spectrum disorder' and 'gender dysphoria/gender variance'. RESULTS: A total of 12 publications were included. A higher incidence of comorbidity was reported compared to what is epidemiologically expected, starting from an ASD study population and a population of children and adolescents with GD/GV. The results should be interpreted with caution due to methodological limitations in the studies as e.g. in the diagnostic assessment and the frequent lack of a control group. CONCLUSION: The more frequent co-occurrence of ASD and GD/GV has consequences for clinical practice. In both diagnostic and supportive care pathways, it is advisable to recognize and acknowledge both conditions and to work out an adapted pathway. More targeted research into specific characteristics in this group is necessary in order to fine-tune (mental) health care and long-term perspectives.

The influence of host tissue on M. gallisepticum vlhA gene expression.

Mycoplasma gallisepticum, a significant poultry pathogen, has evolved rapidly in its new passerine host since its first reported isolation from house finches in the US in 1994. In poultry, M. gallisepticum infects the upper respiratory tract, causing tracheal mucosal thickening and inflammation, in addition to inflammation of the reproductive tract. However, in house finches M. gallisepticum primarily causes inflammation of the conjunctiva. Given that different tissues are primarily affected by the same pathogen in different hosts, we have compared the early changes in gene expression of the phase-variable lipoproteins (vlhA) gene family of M. gallisepticum collected directly from target tissues in both hosts. Previous data have demonstrated that vlhA genes may be related to virulence, exhibiting changes in expression in a non-stochastic, temporal progression and we hypothesize that this may be influenced by differences in the target host tissue. If this is true, we would expect M. gallisepticum to display a different vlhA gene expression pattern in the chicken trachea compared to its expression pattern in house finch conjunctiva. Here we report significant differences in vlhA gene expression patterns between M. gallisepticum collected from chicken tracheas compared to those collected from house finch conjunctiva. While many of the predominant vlhA genes expressed in the input population showed an increase in expression in the chicken trachea at day one postinfection, those same vlhA genes decreased in expression in the house finch. These data suggest that discrete suites of vlhA genes may be involved in M. gallisepticum pathogenesis and tropism for unique tissues in two disparate avian hosts.

[A young boy with periodic strange behavior and hypersomnia: Kleine-Levin syndrome]. / Een puber met periodiek vreemd gedrag en slaperigheid: syndroom van Kleine-Levin.

Kleine-Levin syndrome is a rare neuro-psychiatric disease. Most of the young patients are males who present with hypersomnia, cognitive dysfunction, altered perception, eating disorder (e.g. hyperphagia) or disinhibited behaviour (e.g. hypersexuality). Psychiatric symptoms such as apathy, delusions and hallucinations, depressed mood and compulsive behaviours also appear often and result frequently in a psychiatric referral. These symptoms, however, should be distinguished from those of psychiatric diseases as early as possible in order to ensure that patients do not receive the wrong treatment. We present the case of an 11-year-old boy in whom the psychiatric symptoms were initially the most prominent ones.

Attenuated Phenotype of a Recent House Finch-Associated Mycoplasma gallisepticum Isolate in Domestic Poultry.

Mycoplasma gallisepticum, known primarily as a respiratory pathogen of domestic poultry, has emerged since 1994 as a significant pathogen of the house finch (Haemorhousmexicanus) causing severe conjunctivitis and mortality. House finch-associated M. gallisepticum (HFMG) spread rapidly and increased in virulence for the finch host in the eastern United States. In the current study, we assessed virulence in domestic poultry with two temporally distant, and yet geographically consistent, HFMG isolates which differ in virulence for house finches-Virginia 1994 (VA1994), the index isolate of the epidemic, and Virginia 2013 (VA2013), a recent isolate of increased house finch virulence. Here we report a significant difference between VA1994 and VA2013 in their levels of virulence for chickens; notably, this difference correlated inversely to the difference in their levels of virulence for house finches. VA1994, while moderately virulent in house finches, displayed significant virulence in the chicken respiratory tract. VA2013, while highly virulent in the house finch, was significantly attenuated in chickens relative to VA1994, displaying less-severe pathological lesions in, and reduced bacterial recovery from, the respiratory tract. Overall, these data indicate that a recent isolate of HFMG is greatly attenuated in the chicken host relative to the index isolate, notably demonstrating a virulence phenotype in chickens inversely related to that in the finch host.

Evaluation of the hypothalamic-pituitary-adrenal axis and its relationship with central respiratory dysfunction in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi Syndrome (PWS) have been considered at risk for central adrenal insufficiency (CAI). Hypothalamic dysregulation has been proposed as a common mechanism underlying both stress-induced CAI and central respiratory dysfunction during sleep. OBJECTIVE: To evaluate CAI and sleep-related breathing disorders in PWS children. PATIENTS AND METHODS: Retrospective study of cortisol response following either insulin tolerance test (ITT) or glucagon test (GT) in 20 PWS children, and comparison with 33 non- Growth Hormone deficient (GHD) controls. Correlation between sleep related breathing disorders and cortisol response in 11 PWS children who received both investigations. RESULTS: In PWS children, the cortisol peak value showed a significant, inverse correlation with age (Kendall's τ = -0.411; p = 0.012). A similar though non-significant correlation was present between cortisol increase and age (τ = -0.232; p = 0.16). Similar correlations were found in controls. In only 1 of 20 PWS children (5 %), ITT was suggestive of CAI. Four patients had an elevated central apnea index but they all exhibited a normal cortisol response. No relationship was found between peak cortisol or cortisol increase and central apnea index (respectively p = 0.94 and p = 0.14) or the other studied polysomnography (PSG) parameters. CONCLUSIONS: CAI assessed by ITT/GT is rare in PWS children. Our data do not support a link between CAI and central respiratory dysregulation.

Neuropsychological functioning related to specific characteristics of nocturnal enuresis.

INTRODUCTION/BACKGROUND: There is a high comorbidity demonstrated in the literature between nocturnal enuresis and several neuropsychological dysfunctions, with special emphasis on attention deficit hyperactivity disorder (ADHD). However, the majority of the psychological studies did not include full non-invasive screening and failed to differentiate between monosymptomatic nocturnal enuresis (MNE) and non-MNE patients. OBJECTIVE: The present study primarily aimed to investigate the association between nocturnal enuresis and (neuro)psychological functioning in a selective homogeneous patient group, namely: children with MNE and associated nocturnal polyuria (NP). Secondly, the study investigated the association between specific characteristics of nocturnal enuresis (maximum voided volume, number of wet nights and number of nights with NP) and ADHD-inattentive symptoms, executive functioning and quality of life. STUDY DESIGN: The psychological measurements were multi-informant (parents, children and teachers) and multi-method (questionnaires, clinical interviews and neuropsychological testing). RESULTS: Thirty children aged 6-16 years (mean 10.43 years, SD 3.08) were included. Of them, 80% had at least one psychological, motor or neurological difficulty. The comorbid diagnosis of ADHD, especially the predominantly inattentive presentation, was most common. According to the teachers, a low maximum voided volume (corrected for age) was associated with more attention problems, and a high number of nights with NP was associated with more behaviour-regulation problems. No significant correlations were found between specific characteristics of enuresis and quality of life. Details are demonstrated in Table. DISCUSSION: The children were recruited from a tertiary referral centre, which resulted in selection bias. Moreover, NP was defined as a urine output exceeding 100% of the expected bladder capacity for age (EBC), and not according to the expert-opinion-based International Children's Continence Society norm of 130% of EBC. The definition for NP of a urine output exceeding 100% of the EBC is more in line with the recent findings of the Aarhus group. CONCLUSIONS: For children with MNE and associated NP, a high comorbidity with the predominantly inattentive presentation of ADHD was demonstrated. Children experienced problems with daytime functioning in relation to their wetting problem at night. According to the teachers, a low maximum voided volume was associated with more attention problems, and a high number of nights with NP was associated with more behaviour-regulation problems. Although comorbidity is still the appropriate word to use, the observation favours a more complex pathogenesis of enuresis with a common pathway in the central nervous system, including: neurotransmitters, influencing neuropsychological functioning as well as sleep, circadian rhythm of diuresis and bladder function control.

Evidence of trade-offs shaping virulence evolution in an emerging wildlife pathogen.

In the mid-1990s, the common poultry pathogen Mycoplasma gallisepticum (MG) made a successful species jump to the eastern North American house finch Haemorhous mexicanus (HM). Subsequent strain diversification allows us to directly quantify, in an experimental setting, the transmission dynamics of three sequentially emergent geographic isolates of MG, which differ in the levels of pathogen load they induce. We find significant among-strain variation in rates of transmission as well as recovery. Pathogen strains also differ in their induction of host morbidity, measured as the severity of eye lesions due to infection. Relationships between pathogen traits are also investigated, with transmission and recovery rates being significantly negatively correlated, whereas transmission and virulence, measured as average eye lesion score over the course of infection, are positively correlated. By quantifying these disease-relevant parameters and their relationships, we provide the first analysis of the trade-offs that shape the evolution of this important emerging pathogen.

Sleep fragmentation and increased periodic limb movements are more common in children with nocturnal enuresis.

AIM: To determine sleep fragmentation in children with nocturnal enuresis (NE). METHODS: Paediatricians assessed NE parameters in children referred to an enuresis clinic. Control subjects, matched by age and gender and without incontinence or (un)treated NE, were recruited from the paediatric sleep clinic regardless of their sleep problem. Sleep was investigated by one overnight video-polysomnography in both groups. RESULTS: The study group comprised 67 children with proven NE (50 boys and 17 girls between six and 16 years: 11.1 ± 2.8 SD). They were matched with 67 control subjects (47 boys and 20 girls aged between six and 16 years: 11.0 ± 2.9 SD). Children with NE had a higher incidence of periodic limb movements associated with cortical arousals in their sleep. They displayed significant higher periodic limb movement index, arousal index and awakening index than the control group. CONCLUSION: Children with NE displayed higher sleep fragmentation and periodic limb movements in sleep than the control children with a possible sleep disorder without NE. The findings emphasise the central involvement of the pathophysiology of NE and the multifactorial nature of the condition.

[Narcolepsy in children with a psychiatric disorder]. / Narcolepsie bij kinderen met een psychiatrische stoornis.

Children with a psychiatric disorder often have sleep problems. To interpret these problems correctly one needs to conduct a multimodal investigation at three levels: internal, psychiatric and neurological. On the basis of a case study we discuss the differential diagnostic considerations for narcolepsy and a diagnostic protocol for children.

Common garden experiment reveals pathogen isolate but no host genetic diversity effect on the dynamics of an emerging wildlife disease.

Host genetic diversity can mediate pathogen resistance within and among populations. Here we test whether the lower prevalence of Mycoplasmal conjunctivitis in native North American house finch populations results from greater resistance to the causative agent, Mycoplasma gallisepticum (MG), than introduced, recently-bottlenecked populations that lack genetic diversity. In a common garden experiment, we challenged wild-caught western (native) and eastern (introduced) North American finches with a representative eastern or western MG isolate. Although introduced finches in our study had lower neutral genetic diversity than native finches, we found no support for a population-level genetic diversity effect on host resistance. Instead we detected strong support for isolate differences: the MG isolate circulating in western house finch populations produced lower virulence, but higher pathogen loads, in both native and introduced hosts. Our results indicate that contemporary differences in host genetic diversity likely do not explain the lower conjunctivitis prevalence in native house finches, but isolate-level differences in virulence may play an important role.