Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p < 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p < 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders.

Sensory dysregulation in tic disorders is associated with executive dysfunction and comorbidities.

BACKGROUND: Tics are conceptualized as a sensorimotor phenomenon with a premonitory urge typically described by patients. As observed in other neurodevelopmental disorders, we have observed sensory dysregulation symptoms, such as tactile hypersensitivity to clothing, in children with tic disorders; however, formal clinical research in this area is limited. OBJECTIVE: To define the presence of sensory dysregulation symptoms in tic disorders, and their clinical associations. METHODS: Prevalence of sensory dysregulation in 102 children with tic disorders was compared to 61 age- and sex-matched healthy controls. Sensory dysregulation, executive function, and quality of life data were obtained through the Short Sensory Profile-2, Sensory Profile-2, Sensory Processing Measure, Behaviour Rating Inventory of Executive Function-2, and Strength and Difficulties Questionnaire and Pediatric Quality of Life Inventory. Tics were assessed with the Yale Global Tic Severity Scale. RESULTS: Children with tics, in the presence of comorbidity, had elevated sensory dysregulation compared to healthy controls (P < 0.001). There was a positive correlation between sensory dysregulation and global executive difficulties in children with tics and comorbidity (n = 87; rho = 0.716; P < 0.001) and a negative correlation of sensory dysregulation with quality of life (n = 87; rho = -0.595; P < 0.001). In children with tics, there was an association between sensory dysregulation and number of comorbidities (P < 0.001). CONCLUSION: In the presence of comorbidity, children with tic disorders have broad sensory dysregulation symptoms beyond the premonitory urge. There was a statistically significant association between sensory dysregulation and executive function difficulties and the presence of neurodevelopmental and psychiatric comorbidity. Sensory dysregulation can be considered neurodevelopmental symptoms, providing insight into the neurobiology of tics and opportunities for therapeutic intervention. © 2019 International Parkinson and Movement Disorder Society.

An exploratory study into an adapted use of the Alert Program for tic disorder in children.

OBJECTIVES: This preliminary study explored whether an adapted approach to the Alert Program, that uses sensorimotor strategies, might assist with management of tic disorders in children. The Alert Program, a program that uses sensorimotor strategies for self-regulation in children with neurodevelopmental disorders, had not been trialled with children with tic disorders. METHODS: Ten children with tic disorder were assessed using the Dunn Sensory Profile 2 (SP2), the Yale Global Tic Severity Scale (YGTSS) and the Parent Tic Questionnaire (PTQ). Participants attended three 60-90-minute appointments with an occupational therapist and clinical psychologist for implementation of the adapted Alert Program. RESULTS: The YGTSS showed tic reduction in all participants. The total YGTSS pre-intervention mean score of 46.5 improved to 17.7 post-therapy. Five participants reported no impairment post-therapy. PTQ scores reduced in nine participants. On the SP2, 30% of participants scored as having sensory sensitivities that impaired daily function. CONCLUSIONS: This exploratory study found trialling an adapted approach to the Alert Program that uses sensorimotor-based approach decreased tic severity in children with tic disorders. A randomised controlled trial is needed to establish the effectiveness and feasibility of this approach.

Counselling of complications of termination of pregnancy within a single Trust setting.

BACKGROUND: National guidelines on the care of women requesting induced abortion recommend that counselling prior to termination of pregnancy (TOP) includes information about potential complications and sequelae. Case notes of women requesting TOP in a single hospital Trust were audited for documentation of counselling about complications. As a result of this audit the integrated care pathway (ICP) was altered to include a list of the potential complications and sequelae. We repeated the audit to evaluate the effect of this intervention on counselling. OBJECTIVE: To re-audit the counselling of women undergoing TOP with regard to the potential complications and sequelae of TOP and to compare counselling in consultant-led and nurse-led clinics. METHODS: The study population comprised women requesting TOP within south Glasgow, UK who were seen in a consultant-led gynaecology clinic or nurse-led clinic. A retrospective audit was carried out in 2004 and a prospective audit in 2005. Case notes and correspondence to primary care referrers were reviewed for documented evidence of counselling. RESULTS: We reviewed 98% of case notes in the first audit and 85% in the second audit. Results from both nurse-led and consultant-led clinics indicated that evidence of adequate counselling had improved, with an increase from 98% to 100% in the nurse-led clinics and from 43% to 64% in the consultant-led clinics. CONCLUSIONS: Comparison of results from 2004 and 2005 suggests improvement in counselling since introduction of an ICP listing complications and sequelae of TOP.

Evaluation of transobturator tension-free vaginal tapes in management of women with recurrent stress urinary incontinence.

OBJECTIVES: To assess the efficacy of transobturator tapes in the treatment of women with recurrent urodynamic stress incontinence. METHODS: We performed a secondary analysis of a prospective, randomized, single-blinded study. A total of 341 women were recruited (April 2005 and April 2007) and randomly assigned to undergo "inside-out" TVT-O or "outside-in" TOT-ARIS. Of these women, 46 had undergone ≥1 previous continence procedures and were included in the present study. The preoperative assessment included a urodynamic assessment and completion of validated symptom severity and quality-of-life questionnaires. The primary outcome was the patient-reported success rate at 1 year as assessed using the Patient Global Impression of Improvement (very much/much improved). The secondary outcomes included changes in quality of life, sexual function, the objective success rates defined as negative findings on the standard 1-hour pad test, and a comparison between both routes of transobturator tapes. Multivariate analysis was performed to identify the risk factors for failure. RESULTS: All 46 women completed the 1-year follow-up period. The patient-reported success rate and objective cure rate was 69.6% and 76.5%, respectively, with no significant differences between the 2 transobturator routes (P = .104, odds ratio [OR] 2.933, 95% confidence interval [CI] 0.803-10.719; and P = .077, OR 4.524, 95% CI 0.849-24.109, respectively). Of the 46 women, 35 (76.1%) reported >10-point improvement on the total King's Health Questionnaire scores and 71% of sexually active women (n = 22) showed an improvement in the total 12-item Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire scores. On multivariate analysis, a maximal urethral closure pressure of <30 cm H(2)O was the only independent risk factor for failure (P = .016, OR 9.206, 95% CI 1.511-56.104). CONCLUSIONS: Transobturator tapes have good patient-reported and objective success rates at 1 year of follow-up in women with previous failed incontinence surgery. A low maximal urethral closure pressure was the only independent predictor of failure.

Evaluation of transobturator tapes (E-TOT) study: randomised prospective single-blinded study comparing inside-out vs. outside-in transobturator tapes in management of urodynamic stress incontinence: short term outcomes.

OBJECTIVES: To compare the "inside-out (TVT-O)" vs. "outside-in (ARIS)" transobturator tapes in the management of female urodynamic stress incontinence (USI) and to identify independent risk factors of failure of transobturator tapes. STUDY DESIGN: A prospective, single blinded, randomised trial. Women undergoing transobturator tapes as sole procedure in the period April 2005 and April 2007 were randomised to TVT-O for the inside-out approach and TOT-ARIS for the outside-in approach. The primary outcome measure at 6 months was the absence of USI on urodynamics. Secondary outcomes included; patient-reported success rates, overall patient satisfaction and peri-operative complications. RESULTS: 341 women were recruited: 171 in the outside-in group and 170 in the inside-out. Severe post-operative thigh pain was twice as common in the inside-out group but this was not statistically significant (6.7% vs. 3.5%, p=0.19). 317 women completed the 6 months follow-up; objective cure rates and patient-reported success rates were 85.4 and 80.5%, respectively, with no significant difference between the groups (p=0.28 and p=0.138, respectively). On multivariate analysis: low maximum urethral closure pressure (MUCP) (<30 cm H2O) and previous incontinence surgery were confirmed as independent risk factors for objective failure of transobturator tape with increased odds of failure of 7.06 (2.85-17.48) and 6.22 (2.34-16.52), respectively. CONCLUSION: This study shows no significant differences in the objective cure rates and patient-reported success rates between the "inside-out (TVT-O)" and "outside-in (ARIS)" transobturator tape procedures in the management of female USI at 6 months follow-up. Previous incontinence surgery and low MUCP were significant risk factors for failure of transobturator tapes.

Surgical management of stress urinary incontinence in Scotland and Wales: a questionnaire study.

Urodynamic stress incontinence is a common complaint. There have been over two hundred procedures described for treatment. In 2003, the Royal College of Obstetricians and Gynaecologists in London published a guideline highlighting the evidence for different surgical approaches. These guidelines are intended to guide practice in the United Kingdom, including the two countries that were surveyed. It was our impression however that more sub-urethral tape type procedures were taking place than was recommended. We therefore undertook a postal survey of the consultant gynaecologists in Scotland and Wales, to compare current practice with the evidence base, and also to assess practice from a clinical and manpower perspective. Two hundred and forty consultants were identified in Scotland (161) and Wales (79). About two-thirds of those who saw patients with stress incontinence would always arrange pre-operative physiotherapy, and the majority of consultants would always organise urodynamics preoperatively. There were several different choices of primary procedure, with Tension Free Vaginal Tape (TVT Gynecare- Johnson & Johnson) the most common option. More than half of the respondents in both countries would refer a patient with recurrent stress incontinence to a specialist. TVT was also the most common choice of procedure for recurrent stress incontinence. The procedures that have a grade A recommendation in the RCOG guideline are Burch colposuspension and TVT, and 72% in Scotland and 63% in Wales would perform one of these procedures as first choice. Clinical practice moves on and there are several new sub-urethral tape procedures available on the market. It is important to balance the available evidence base with new developments in order to optimise the management of this common condition.

The extent and severity of urinary incontinence amongst women in UK GP waiting rooms.

INTRODUCTION: Few women seek help for urinary incontinence. Subsequently, there may be many women accessing primary care services who would benefit from treatment or advice. If high levels of unexpressed need are present in this population, a more proactive approach to continence management may be appropriate, but the feasibility of this depends on an accurate assessment of the level of unmet need in this population. AIM: To assess the prevalence of urinary incontinence in a female population attending primary care and the extent of treatment seeking in relation to level of need. METHODS: A cross-sectional survey of urinary incontinence of adult women attending primary care practices in West Yorkshire, London, Glasgow and Leicestershire during a 10- or 15-day period. RESULTS: Three thousand two hundred and seventy-three (54%) women responded. Twenty-one per cent reported stress urinary incontinence only, 3.5% reported urge incontinence only and 21% reported mixed stress and urge incontinence during the preceding month (9% had moderate or severe symptoms). Fifty-three per cent of these had not consulted a health care professional, which is equivalent to 1 in 20 of women in GP waiting rooms, most of whom have stress and urge incontinence (75%) or stress incontinence only (21%). CONCLUSIONS: Nearly half of female primary care attendees had experienced incontinence during the preceding month, but only a minority had sought help. Even amongst the nearly 1 in 10 women with moderate or severe incontinence only about half had sought help. There remains considerable health decrement due to urinary incontinence in those not receiving help in a population readily accessible to primary care services.