8/13/2019 Clinical features associated with GI symptoms in autism spectrum disorders

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tension-type, migraine or both types of headache. Results: To date, 288 subjects havecompleted follow-up including 88 former well controls and 200 former CAP patients. Themean age at follow-up was 20.2 years and 59% were female. Using chi-square analysis, wefound that headaches were significantly more common in those with FGIDs (58%) comparedto those without FGIDs (38%, p<0.05). Migraine headaches were also significantly morecommon with FGID's (45%) compared to those without FGIDs (30%, p<0.05). There wasnot an association between tension-type headaches and FGIDs (P>0.05). In evaluation of type of FGID and headache type, it appears that migraines are significantly more commonwith functional dyspepsia (51%) compared to those without functional dyspepsia (31%,p<0.05). Migraines were not statistically associated with other FGID types including abdom-inal migraine, IBS, FAP, and FAPS. However, there was a trend between migraines in thosewith IBS (45%) compared to those without IBS (32%, p=0.078). Conclusions: In ourprospective cohort study, there is a statistically significant association between FGID andheadache diagnosis. There also was significant association between migraines and both FGIDand functional dyspepsia. There was a trend between migraines and IBS. Further researchis needed to investigate the pathophysiology of these findings.

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Long Term Prognosis of Children Undergoing HIDA Scan for SuspectedBiliary DyskinesiaSudipta Misra

 We have previously reported short term prognostic value of Hepatobiliary Scintiscan (HIDA)in children suspected to be having functional biliary tract disease. In this abstract we report5 year follow up of the population. Methods: Children undergoing HIDA scan at Children'sHospital of Illinois for chronic abdominal pain, nausea or vomiting between March 1999andFebruary2002 wereanalyzed. Thesechildrenhad inconclusive gastrointestinaldiagnosticworkup including hepatobiliary ultrasound, endoscopies, barium X rays, pH probe studiesetc. Therapeutic trials in some patients with acid suppression, tricyclic antidepressants andanti spasmotics were not successful. HIDA scan was performed according to a standardizedprotocol. A gall bladder ejection fraction of less than 35% was taken to be abnormal. Clinicaldata was collected by retrospective chart review. A scripted telephone survey was done 5years after the initial HIDA scan to document long-term outcome. The data was re analyzed

to compare short and long term prognosis of these children. Results: Forty two of 61 childrenhad abnormal HIDA scan. On telephone follow up at an average interval of 61.9 monthsafter HIDA scan; 19 children (31.1%) had recurrence of symptoms, 33 (54.1%) wereasymptomatic and 9 (14.8%) could not be reached There was no difference between childrenwith normal and abnormal HIDA results in clinical presentations, short term (85.7% and84.2%) and long term (64.9% and 60%) outcomes. Twenty seven of the 42 children withabnormal scan results underwent interventions (21 cholecystectomy only, 4 cholecystectomyfollowed by sphincter of Oddi sphincterotomy and 2 sphincterotomy only). Followingintervention, children with abnormal HIDA scan had better short-term prognosis (88.9%and 54.5%, p=.02) but their long-term prognosis (52.2% and 85.7%, p = .04) was worsethan those without intervention. No clinical prognostic indicator such as location of abdom-inal pain, nausea etc. could be identified. Conclusion: Children with abnormal HIDA scanhad a high rate of long term recurrence after surgical intervention as well as spontaneousresolution of symptoms without intervention. This test was not a good long term prognosticindicator. Hence, HIDA scan result, including undetectable ejection fractions, should beused with caution to select children for surgical intervention in suspected biliary dyskinesia. Focused prospective studies are needed to define biliary dyskinesia in children.

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Clinical Features Associated With GI Symptoms in Autism SpectrumDisorders (ASD)Kent C. Williams, George J. Fuchs, Glenn T. Furuta, Margaret A. Marcon, Daniel L.Coury

Background:  Rates of ASD are estimated at 1 in 91 children(1.1%). While studies reportconflicting results about the prevalence of GI symptoms in children with ASD versus childrenwithout ASD, GI complaints are common in both populations. However, whether GI symp-toms in children with ASD are associated with distinctive clinical features is unclear.  Object-ives:  To determine the frequency of GI symptoms as reported by parents in a large ASDregistry, and to identify clinical features associated with GI symptoms in children with ASD.Methods:   Autism Treatment Network Registry enrolled 1420 children with an ADOS-confirmed ASD diagnosis (autism, Asperger disorder, or PDD-NOS) between September2007 and December 2009 at 15 sites in US and Canada. Parents completed a GI symptominventory, as well as Child Behavior Checklist (CBCL), Child Sleep Health Questionnaire(CSHQ) and Pediatric Quality of Life (PedsQL) at time of enrollment.  Results: GI data wasavailable for 1185 children. At time of enrollment 45% of children displayed GI symptoms.

For GI complaints present within the previous 3 months, constipation was most common(32%) followed by abdominal pain (27%), diarrhea (26%), other (18%), nausea (14%) andbloating (12%). For chronic GI complaints (>3 months duration), constipation was mostcommon (22%) followed by other (14%), abdominal pain (14%), diarrhea (12%), bloating(9%) and nausea (5%). GI symptoms increased with age, ranging from 39% in those under5 years to 51% in those 7 years and older (p<0.0001). Children ages 1 to 5 years with GIsymptoms had higher CBCL t-scores for total problems and for the emotionally reactive,anxious/depressed, somatic complaints, sleep problems, internalizing problems, affectiveproblems, and anxiety problems subscales, all p<0.05. Children age 6 to 18 years with GIsymptoms had higher CBCL t-scores for total problems and for all subscales (p<0.01). Sleepproblems occurred more frequently in children with than those without GI symptoms (50%versus 37%, p<0.0001). Children with GI symptoms also had lower PedsQL scores (overallscore and all five subscales, p<0.01) compared to children without GI problems. Presenceof GI problems did not differ by gender, ASD subtype, race, or IQ.  Conclusions: ParentsofchildrenwithASDreport a high prevalenceof GI symptoms intheirchildren.GI complaintsare associated with age, behavioral abnormalities, sleep disturbances and overall decreasedhealth-related quality of life. Further investigation is needed to clarify these associations and

S-74AGA Abstracts

whether treatment of GI disorders improves behavioral and cognitive function, sleep, andquality of life in ASD children.

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Intestinal Wall Remodeling Measured With Serial CT Enterography in PatientsWith Crohn's Disease Treated With InfliximabDavid H. Bruining, Edward V. Loftus, Eric C. Ehman, Hassan A. Siddiki, Douglas L.Nguyen, Jeff L. Fidler, James E. Huprich, Jayawant N. Mandrekar, William S. Harmsen, William J. Sandborn, Joel G. Fletcher

Background: The use of computed tomography enterography (CTE) in patients (pts) withCrohn's disease has increased at some tertiary care centers. CTE has a high sensitivity andspecificity for active small bowel inflammation, and it may provide an objective measurementof treatment response. There is a paucity of data, however, how radiologic parameters of 

active disease change over time with infliximab therapy, and whether these alterationscorrespond to clinical symptoms, serum biomarkers, or endoscopic appearance. Methods: We retrospectively identified pts with established Crohn's disease who had undergone serialCTE imaging while receiving infliximab. Pts had imaging before and after initiation of infliximab, or two CTEs more than 6 months apart while on maintenance dosing. Data wereanalyzed both per lesion and per pt. Lesions were defined as improved if a decrease inenhancement or length occurred without worsening of other parameters (enhancement,length, vasa recta dilatation/comb sign, fatty proliferation, or stratification). Pt s were groupedas responders (all lesions improved), partial responders (some lesions improved), and non-responders(worsening or no changes in alllesions).In orderto remain in therespondergroup,no worsening could be identified on CTEs subsequent to the initial follow-up examination.Radiologic scoring was performed by a GI radiologist blinded to the clinical information.Clinical symptoms at the time of follow-up CTE was determined by a gastroenterologistblinded to the imaging results. Results: Of the 63 pts identified (52% males), median agewas 37.7 years, median disease duration was 14.9 years, and median time between initialand first follow-up CTE was 356 days. Only 17 patients (27.0%) did not have pre-infliximabCTE imaging for comparison. The most common indications for repeat imaging were re-assessmentof disease activity(79.3%) and pain(17.5%).A totalof 105 lesions wereidentified,52 (49.5%) improved, 11 (10.5%) remained unchanged, and 42 (40.0%) worsened. Per pt,

28 (44.4%) were responders, 12 (19.0%) were partial responders, and 23 (36.5%) werenon-responders. Radiologic response showed a low agreement with clinical symptoms attime of 2nd CTE (Kappa=0.28), endoscopic appearance (Kappa=0.16), and CRP (Kappa=0.39). Conclusion: Radiologic improvement/remodeling was noted in more than half of ptson infliximab therapy, despite a study design that was likely biased towards non-responders. A po or correlation with clinical symptoms, serum biomarkers, and endoscopic appearancesupports the notion that CTE imaging may be a complementary tool to other methods inassessing response to treatment.

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Predicting Response to Infliximab in Crohn's Disease: Role of CRP, MREnterography and NOD2 GenotypeFinlay A. Macrae, Gregor J. Brown, Paula Lewis, Bernadette Viney, Cathy Pizzey, Zina Valaydon, Damien Stella, Robert N. Gibson, Kaye E. Marion

Response to infliximab therapy for Crohn's disease (CD) is unpredictable. We aimed to i)correlate MR enterography (MRE) findings with the CD Activity Index (CDAI) and C ReactiveProtein (CRP) at study entry and exit, ii) determine if entry a) CRP, b) NOD2 genotypingand/or c) MRE could predict response to infliximab as measured by CDAI and MRE, andiii) correlate changes in MRE with changes in CRP and CDAI in response to treatment.Methods: 29 consentingpatientswith ileal CD,CDAI >220 and clinically assessed as requiringinfliximab were recruited. NOD2 genotyping and, at entry and exit (at 26 weeks), MRE (theprimary endpoint), CDAI, and CRP assessments were done. 24 completed the study; 4withdrew for surgery and 1 moved overseas. Disease remission and response were definedas CDAI<151 and a reduction in CDAI>100 respectively at study end. 3 infliximab infusionswere administered for induction. Relationships assessed were: CDAI with CRP at entry andexit; NOD2 mutational status with CDAI change during treatment; MRE parameters withCDAI and CRP at entry and exit; and entry MRE parameters (length of affected bowel;presence of strictures; wall thickness and contrast enhancement; and global MR assessmentof disease activity) with changes in CDAI (remission and/or response) and CRP duringtreatment. Results: Of the 24 patients, 15 entered remission and 6 more responded. All but6 patients normalized CRP with treatment. i) There was no correlation between the CDAIand CRP at entry or exit; iia) CRP at baseline did not predict remission or response toinfliximab. iib) 5/21 had pathogenic mutations in NOD2; the median CDAI change forpatients with mutations was 293 compared with 224 for those without mutations. iic) Onglobal MRE assessment, 5 of 23 evaluable patients normalized findings at exit MRE, 5

improved and 13 had no change between entry and exit. Improvement in CDAI was greaterfor patients with fewer strictures at entry (p=0.04) whereas bowel wall thickening and lengthof bowel affected did not significantly predict response. iii) MRE global response correlatedwith changes in CDAI (p=0.04) but not CRP. Conclusion: As elsewhere, we found nocorrelation of CDAI with CRP. Patients with NOD2 mutations had a greater fall in CDAIthan those without NOD2 mutations. Global MRE assessment of response correlated withCDAI changes; multiplicity of strictures predicted a poor response to infliximab. MREparameters at exit identified continuing disease more sensitively than CDAI, supportingcontinuation of treatment beyond symptomatic response (i.e. CDAI).