Dipesh H. Vasant

Val66Met in Brain-Derived Neurotrophic Factor Affects Stimulus-Induced Plasticity in the Human Pharyngeal Motor Cortex

BACKGROUND & AIMS Polymorphisms in brain-derived neurotrophic factor (BDNF) can affect brain and behavioral responses. However, little is known about the effects of a single nucleotide polymorphism (SNP) in BDNF, at codon 66 (the Val-Met substitution, detected in approximately 33% of the Caucasian population) on stimulation-induced plasticity in the cortico-bulbar system. We examined whether this SNP influenced outcomes of different forms of neurostimulation applied to the pharyngeal motor cortex. METHODS Thirty-eight healthy volunteers were assessed for corticobulbar excitability after single-pulse, transcranial magnetic stimulation of induced pharyngeal electromyographic responses, recorded from a swallowed intraluminal catheter. Thereafter, volunteers were conditioned with pharyngeal electrical stimulation, or 2 forms of repetitive (1 and 5 Hz) transcranial magnetic stimulation (rTMS). Repeated measurements of pharyngeal motor-evoked potentials were assessed with transcranial magnetic stimulation for as long as 1 hour after the 3 forms of neurostimulation and correlated with SNPs at codon 66 of BDNF (encoding Val or Met). RESULTS Pharyngeal electrical stimulation significantly increased the amplitude of motor-evoked potentials in individuals with the SNP that encoded Val66, compared to those that encoded Met66, with a strong GENOTYPE*TIME interaction (F₈,₁₁₂ = 2.4; P = .018). By contrast, there was a significant reduction in latencies of subjects with the SNP that encoded Met66 after 5-Hz rTMS (F₃,₆₀ = 4.9; P = .04). In addition, the expected inhibitory effect of 1-Hz rTMS on amplitude was not observed in subjects with the SNP that encoded Met66 in BDNF (F₇,₁₄₀ = 2.23; P = .035). CONCLUSIONS An SNP in human BDNF at codon 66 affects plasticity of the pharyngeal cortex to different forms of neurostimulation. Genetic analysis might help select specific forms of neurostimulation as therapeutics for patients with disorders such as dysphagic stroke.

Pharyngeal Electrical Stimulation in Dysphagia Poststroke A Prospective, Randomized Single-Blinded Interventional Study

Background. Pharyngeal electrical stimulation (PES) appears to promote cortical plasticity and swallowing recovery poststroke. Objective. We aimed to assess clinical effectiveness with longer follow-up. Methods. Dysphagic patients (n = 36; median = 71 years; 61% male) recruited from 3 trial centers within 6 weeks of stroke, received active or sham PES in a single-blinded randomized design via an intraluminal pharyngeal catheter (10 minutes, for 3days). The primary outcome measure was the Dysphagia Severity Rating (DSR) scale (<4, no-mild; ≥4, moderate-severe). Secondary outcomes included unsafe swallows on the Penetration-Aspiration Scale (PAS ≥ 3), times to hospital discharge, and nasogastric tube (NGT) removal. Data were analyzed using logistic regression. Odds/hazard ratios (ORs/HRs) >1 for DSR <4, hospital discharge, and NGT removal and OR <1 for PAS ≥3, indicated favorable outcomes for active PES. Results. Two weeks post–active PES, 11/18 (61%) had DSR <4: OR (95% CI) = 2.5 (0.52, 14). Effects of active versus sham for secondary outcomes included the following: PAS ≥3 at 2 weeks, OR (95% CI) = 0.61 (0.27, 1.4); times to hospital discharge, 39 days versus 52 days, HR (95% CI) = 1.2 (0.55, 2.5); NGT removal 8 versus 14 days, HR (95% CI) = 2.0 (0.51, 7.9); and DSR <4 at 3 months, OR (95% CI) = 0.97 (0.13, 7.0). PES was well tolerated, without adverse effects or associations with serious complications (chest infections/death). Conclusions. Although the direction of observed differences were consistent with PES accelerating swallowing recovery over the first 2 weeks postintervention, suboptimal recruitment prevents definitive conclusions. Our study design experience and outcome data are essential to inform a definitive, multicenter randomized trial.

PTU-122 A National Survey of GI Physiology & Motility Services in The UK and Ireland

Introduction Clinical demands and advances in diagnostics and therapeutics have seen a rapid growth in GI physiology/motility services. We surveyed the practice, training and attitudes towards services nationally, to determine if these aspects have kept pace with expansion and to identify areas for development. Methods An online survey developed by a multi-disciplinary panel with medical, surgical and GI physiology representation was circulated to all GI clinicians and physiologists in the UK & Ireland by their national societies BSG, AGIP, AUGIS and ACPGBI. The survey included both generic questions and specific ones signposted for ‘specialists’ (GI physiologists/clinical leads). Results 313 responses (59% Gastroenterologists) were received, with 221/313 (71%) from 98 institutions having an on-site GI physiology unit. Most units (88/98) had a clinical lead (60% Gastroenterologists, 34% with ‘subspecialty interest’). Figure 1 summarises the services available nationally. GI physiologists/nurse specialists conduct the majority of studies (69%) and biofeedback (84%). GI physiologists report most studies (Upper GI 71%, Lower GI 69%), however cases are often discussed with a lead clinician prior to finalising (Upper GI: 34% discuss all cases and 38% selected cases; Lower GI: 27% discuss all cases and 27% selected cases), 45% have dedicated multidisciplinary team meetings (MDT) for reporting (held weekly in 72%) and of those without an MDT, 72% felt introducing one would improve provision of therapeutic recommendations. 54% of ‘specialists’ reported that therapeutic recommendations are not routinely made (50% citing reasons such as; no subspecialist clinician/ ‘not qualified’ or ‘not necessary’). Moreover, 70% of ‘specialists’ felt a ‘subspecialist’ clinician is best placed to make such recommendations, whilst only 4% of clinicians without subspeciality interest are comfortable interpreting the data. Overall, very few felt that services (26%), research opportunities (15%) and training (14% for GI physiologists and 10% for clinicians) were adequate, with most GI physiologists (83%) and clinicians (96%) recommending changes with suggestions including an accredited clinical training programme.Abstract PTU-122 Figure 1 Conclusion The survey highlights that GI physiology/motility is a rapidly emerging sub-specialty with limited exposure during clinical training. An MDT approach with subspecialist clinical input facilitates interpretation of complex data and provision of therapeutic recommendations. Percieved deficiencies in current services and training systems have been identified, providing an opportunity to raise awareness nationally via AGIP/BSG and to build on existing training pathways. Disclosure of Interest None Declared

Cerebral Cortical Control of Deglutition

The human swallowing musculature is coordinated centrally through a multidimensional hierarchy of deglutative centres both in the cerebral cortex and brain stem. The cortex has an important role in initiation of the volitional swallow and has a role in all three phases of deglutition. Developments in technology, particularly functional brain imaging, have seen a fuller delineation of the human swallowing network and studies have shown that this system is adaptable to stimuli and subject to plastic change both to internal and external inputs. There is evidence to suggest cortical functional asymmetry, with a dominant swallowing hemisphere in healthy individuals, and when this is affected by stroke, with the non-dominant hemisphere clinically thought to be relevant in re-organisation and recovery of swallowing function. Finally, there is now considerable interest in neuromodulatory-based techniques in driving this brain re-organisation after cerebral injury.

Clinical and histological resolution of collagenous sprue following gluten-free diet and discontinuation of non-steroidal anti-inflammatory drugs (NSAIDs)

Collagenous sprue is a rare small bowel enteropathy that has overlapping clinical features with coeliac disease; it is commonly associated with arthritic autoimmune conditions, which often require non-steroidal anti-inflammatory drugs (NSAIDs). In the limited published literature available, there are putative suggestions of a link between NSAID use and collagen deposition in intestinal subepithelia in such patients. The authors present a case of a 43-year-old woman with long-standing NSAID use for autoimmune polyarthropathy and positive coeliac antibodies. However, distal duodenal biopsies revealed a thickened band of subepithelial collagen with villous atrophic appearances consistent with collagenous sprue. The patient was treated with a gluten-free diet and her NSAIDs were discontinued. After 6 months, her gastrointestinal symptoms had resolved with complete histological resolution of the collagenous subepithelial bands and villous atrophy on duodenal biopsy.

Competency based medical education in gastrointestinal motility-the UK perspective

Dear Editors, We read the article by Yadlapati et al.1 with interest and strongly agree with the authors on the need to introduce competency based medical education (CBME) in gastrointestinal motility diagnostics. In North America, minimum standards in the GI fellowship core curriculum and the ANMS clinical training programme for select trainees have at least ensured that most fellows have the opportunity to observe and interpret motility studies during training.2,3 By contrast in the UK, where the core Gastroenterology training curriculum lacks minimum standards in GI motility, training opportunities appear to be virtually nonexistent and trainees have reported a worrying lack of basic knowledge such as the indications for commonly requested investigations.4 Consistent with the observations of the authors,1 data from a large national survey among GI clinicians and Physiologists in the UK and Ireland5 has identified deficiencies in knowledge,6 a marked variation in practice and quality in GI motility services, further highlighting the implications of the current lack of CBME. The UK survey of 313 respondents representing 98 motility labs has shown that GI clinician input in motility study reporting is infrequent and that therapeutic recommendations are provided by fewer than half of those who report studies.5 The most common reasons for not providing therapeutic recommendations included respondents not feeling ‘qualified’ or that there was ‘no subspecialty clinician’.5 Furthermore, only 4% of 163 nonspecialist GI clinicians surveyed are able to interpret motility study data themselves.5 Provision of therapeutic recommendations from diagnostic tests should be a standard of care and these data highlight an acute need for improved core training in motility investigations for Gastroenterologists and an alternative advanced subspecialty training pathway. In terms of ensuring competency, one successful example of CBME in Gastroenterology that we can learn from is the successful introduction of a national online webbased portfolio system for UK endoscopy training which uses workplace based assessments including standardized direct observation of procedural skills (DOPs).7 This system has also proven to be a resource in terms of understanding trainee learning curves for achieving competency.8 Interestingly, the UK Scientist Training Programme for GI physiologists already uses online assessment tools which include DOPs for GI motility procedures.9 Direct observation of procedural skills with internationally agreed standards could potentially be introduced alongside the novel webbased learning methods described by Yadlapati et al.1 in a portfolio system to deliver much needed CBME in this field. ACKNOWLEDGMENTS

Anorectal Dysfunction in Distal Ulcerative Colitis: Challenges and Opportunities for Topical Therapy.

We read with interest the intriguing report on rectal hypersensitivity in quiescent ulcerative colitis [UC] by Casanova and colleagues.1 Anorectal dysfunction causing urgency, tenesmus, and incontinence are particularly distressing symptoms of dysmotility in UC, which, although most pronounced during active disease, are often present in quiescent and long-standing disease. Reduced rectal wall compliance, and the resultant increased stiffness and rectal narrowing with widening of the pre-sacral space secondary to proliferation of peri-rectal fat, are other possible reasons for such symptoms in the absence of inflammation.2 Furthermore, reduced maximal tolerable balloon volume …

OC-066 A National Survey of the Practice and Attitudes Towards Investigations and Biofeedback Therapy for Anorectal Disorders

Introduction Recent international consensus guidelines on anorectal disorders from the Neurogastroenterology and Motility societies (ANMS-ESNM) recommend biofeedback therapy (BFT) for constipation with dyssynergic defecation (DD) and for faecal incontinence (FI).1 We conducted a national survey to understand the current practice and opinions on anorectal function tests and BFT in the UK & Ireland. Methods An online survey was developed by a multi-disciplinary panel with medical, surgical and GI physiology representation. All GI clinicians and physiologists/scientists in the UK & Ireland were invited to take the survey through their national societies BSG, AGIP, AUGIS and ACPGBI. All respondents were asked about their views on anorectal function tests and BFT, whilst GI physiologists and lead clinicians regularly involved in these studies were asked specific questions relating to their clinical practice. Results 313 responses (59% Gastroenterologists) included representatives from 98 GI physiology units. Of the units surveyed, 74% have anorectal manometry (ARM) (High Resolution 35%), 59% offer BFT and most have access to other imaging modalities (endoanal ultrasound 64%, colonic transit studies 86% and defecating proctography 67%). Overall, the majority agreed that anorectal function tests are useful in managing chronic functional constipation (FC) (69%) and FI (76%). In FI, 61% found BFT helpful, whereas opinions were divided in constipation with 52% finding BFT helpful for all forms of FC and 47% indicating BFT is only helpful in the DD sub-group. Surprisingly, a high proportion of respondents ‘did not know’ how useful anorectal function tests (FC 22% and FI 21%) and BFT (FC 26%, DD 33%, FI 31%) were. Responses from GI physiologists/lead clinicians (n = 95) indicated that; 58% have separate rooms for lower GI studies and the numbers of ARMs performed/month in their units (where known) were; none in 20%, 1–20 cases in 37% and >20/month in 28% and similarly numbers of BFTs/month for DD, FC or FI were; none in 37%, 1–20 cases in 21%, >20 in 18%. Only half the GI physiologists/lead clinicians surveyed offer BFT (FI 52%, DD 53% and FC 47%). Conclusion Whilst anorectal function tests are available in most units, BFT appears to be limited to specialist centres, with the majority agreeing that these interventions are useful in managing FC, DD and in particular FI. Up to a third were unsure about the utility of tests and BFT suggesting a worrying lack of knowledge and exposure amongst non-specialists which could affect the management of patients with these common anorectal disorders. Reference 1 Rao S, et al. NMO 2015;27(5):594–609. Disclosure of Interest None Declared

Gastrointestinal Dysmotility: A qualitative exploration of the journey from symptom onset to diagnosis

Gastrointestinal dysmotility (GID) covers a spectrum of disorders disrupting enteric neuromuscular co‐ordination which, when severe, causes intractable gastrointestinal symptoms and malnutrition and is a recognized cause of chronic intestinal failure. To date, no study has provided an in‐depth account of the experiences of patients with severe GID and their psychosocial needs. This study aimed to explore patients’ experiences from symptom onset and the process of seeking and receiving a diagnosis. It specifically explored the psychological effect of this process and the effect on relationships.

Apprenticeship-based training in neurogastroenterology and motility

ABSTRACT Introduction: Although neurogastroenterology and motility (NGM) disorders affect 50% of patients seen in clinics, many gastroenterologists receive limited NGM training. One-month apprenticeship-based NGM training has been provided at ten centers in the USA for a decade, however, outcomes of this training are unclear. Our goal was to describe the effectiveness of this program from a trainees perspective. Areas covered: We describe the training model, learning experiences, and outcomes of one-month apprenticeship-based training in NGM at a center of excellence, using a detailed individual observer account and data from 12 consecutive trainees that completed the program. During a one-month training period, 302 procedures including; breath tests (BT) n = 132, anorectal manometry (ARM) n = 29 and esophageal manometry (EM) n = 28, were performed. Post-training, all trainees (n = 12) knew indications for motility tests, and the majority achieved independence in basic interpretation of BT, EM and ARM. Additionally, in a multiple-choice NGM written-test paper, trainees achieved significant improvements in test scores post-training (P = 0.003). Expert commentary: One-month training at a high-volume center can facilitate rapid learning of NGM and the indications, basic interpretation and utility of motility tests. Trainees demonstrate significant independence, and this training model provides an ideal platform for those interested in sub-specialty NGM.