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Sutkus LT, Sommer KM, Li Z, Sutton BP, Donovan SD, Dilger RN. Experimentally induced colitis impacts myelin development and home-cage behavior in young pigs regardless of supplementation with oral gamma-cyclodextrin-encapsulated tributyrin. Front Neurosci 2025; 19:1484497. [PMID: 40231172 PMCID: PMC11994669 DOI: 10.3389/fnins.2025.1484497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 03/13/2025] [Indexed: 04/16/2025] Open
Abstract
Introduction Colitis, a chronic intestinal disorder that causes inflammation of the colonic mucosa, has been linked with structural brain abnormalities. To combat intestinal inflammation, researchers have investigated how nutritional supplementation, such as butyric acid, may ameliorate untoward effects. By encapsulating and using conjugates of butyrate, such as butyrate glycerides (i.e., tributyrin), slower release to the lower portions of the gastrointestinal tract can be achieved. Additionally, butyrate supplementation has been linked with supporting brain function and regulating integrity. Methods In the present study, a total of 24 intact male pigs were artificially reared and randomly assigned to 1 of 3 treatment conditions: (1) a control milk replacer (CON), (2) control plus oral dextran sodium sulfate (DSS) to induce colitis, or (3) control supplemented with 9.0 mM of gamma-cyclodextrin encapsulated tributyrin (TBCD) plus oral DSS (TBCD+DSS). Pigs were orally administered DSS treatments daily from postnatal day (PND) 14-18. Continuous video recording began on PND 3 and ceased on PND 27 or 28, with videos processed and analyzed for home-cage tracking behavior. On PND 26 or 27, pigs underwent neuroimaging procedures to assess overall brain anatomy (MPRAGE), microstructure (DTI), and myelin (MWF). Results and discussion Home-cage spatial preference was not altered prior to DSS dosing or during the overall study period. However, TBCD+DSS pigs spent less (p < 0.05) time within quadrant 4 when compared with CON pigs. Across almost all 29 brain regions assessed, absolute volumes were observed to be smaller in the TBCD+DSS group compared with CON and DSS groups. However, once individual volumes were assessed relative to the whole brain, most treatment effects dissipated other than for gray matter volume (p = 0.041). Diffusivity was found to be altered in several regions across treatment groups, thereby indicating differences in fiber organization. In areas like the hippocampus and thalamus, when fractional anisotropy (FA) values were highest for a given treatment, in the other diffusion metrics (mean, radial, axial diffusivity) values were lowest for that same treatment, indicating more organized cellular structure. Several other diffusion trends and differences were observed across various regions. Lastly, myelin water fraction (MWF) values were lowest in DSS-treated groups compared with CON (p < 0.05) for the whole brain and left/right cortices. Conclusion Overall, fiber organization and myelination were observed to be altered by experimentally induced colitis and contrary to expectations, tributyrin supplementation did not ameliorate these effects. Future work is warranted to investigate other protective nutritional mechanisms for colitis.
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Affiliation(s)
- Loretta T. Sutkus
- Neuroscience Program, University of Illinois, Urbana, IL, United States
| | - Kaitlyn M. Sommer
- Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
| | - Zimu Li
- Neuroscience Program, University of Illinois, Urbana, IL, United States
| | - Bradley P. Sutton
- Neuroscience Program, University of Illinois, Urbana, IL, United States
- Department of Bioengineering, University of Illinois, Urbana, IL, United States
- Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, IL, United States
| | - Sharon D. Donovan
- Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL, United States
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
| | - Ryan N. Dilger
- Neuroscience Program, University of Illinois, Urbana, IL, United States
- Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
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Zhou J, Zhu Y, Liu Y, Zhan H, Niu P, Chen H, Zhang J. Proportion and risk factors for hospital-acquired venous thromboembolism in children: a systematic review and meta-analysis of data from 20 million individuals in 22 countries. Res Pract Thromb Haemost 2024; 8:102541. [PMID: 39398295 PMCID: PMC11470410 DOI: 10.1016/j.rpth.2024.102541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/22/2024] [Accepted: 07/30/2024] [Indexed: 10/15/2024] Open
Abstract
Background Hospital-acquired venous thromboembolism (HA-VTE) in children has been widely regarded. Objectives We aimed to analyze the proportion and risk factors for HA-VTE in hospitalized children. Methods We conducted a comprehensive systematic search across 4 databases from 1990 to 2023. Cochran Q test was used to evaluate the heterogeneity of the effect sizes of study, and I2 statistic was used to quantify the heterogeneity. Pooled estimates were calculated by the inverse-variance weighted method in a fixed-effect model or a random-effect model when heterogeneity was low (I2 < 25%) or high (I2 > 25%), respectively. Results In total, 105 original papers and 20,718,294 patients were included in the study, and the proportion of HA-VTE in children was 4.1% (95% CI, 2.9%-5.2%). Although the proportion of venous thromboembolism increased over the various research periods, the differences were not statistically significant. In the subgroup analysis based on country, the proportion of pediatric HA-VTE was lowest in the United Kingdom and highest in Spain, whereas when based on region, the proportion was lowest in Asia and highest in North America. Multiple HA-VTE risk factors were identified, including central venous catheter use, age of >10 years, surgery, injury, infection, obesity, mechanical ventilation, blood transfusion, malignancy, coagulation and hemorrhagic disorders, and length of hospital stay. Conclusion In this study, we systematically analyzed the proportion and risk factors of HA-VTE in hospitalized children. Our findings provide valuable insights for the prevention and treatment of HA-VTE in pediatric patients.
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Affiliation(s)
- Jintuo Zhou
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Yanting Zhu
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Ying Liu
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Hairong Zhan
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Peiguang Niu
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Huajiao Chen
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Jinhua Zhang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
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Gong ZZ, Li T, Yan H, Xu MH, Lian Y, Yang YX, Wei W, Liu T. Exploring the autophagy-related pathogenesis of active ulcerative colitis. World J Clin Cases 2024; 12:1622-1633. [PMID: 38576744 PMCID: PMC10989433 DOI: 10.12998/wjcc.v12.i9.1622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 01/23/2024] [Accepted: 02/27/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND The pathogenesis of ulcerative colitis (UC) is complex, and recent therapeutic advances remain unable to fully alleviate the condition. AIM To inform the development of novel UC treatments, bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC. METHODS The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria. Differential analysis was conducted to obtain differentially expressed genes (DEGs). Autophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes (DEARGs) associated with active UC. DEARGs were then subjected to KEGG, GO, and DisGeNET disease enrichment analyses using R software. Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm. The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs, and the top five targets in the Dgree ranking were designated as core targets. RESULTS A total of 4822 DEGs were obtained, of which 58 were classified as DEARGs. SERPINA1, BAG3, HSPA5, CASP1, and CX3CL1 were identified as core targets. GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy. KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways. Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion. Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls. CONCLUSION Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.
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Affiliation(s)
- Zhuo-Zhi Gong
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
| | - Teng Li
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
| | - He Yan
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
| | - Min-Hao Xu
- College of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Beijing 100102, China
| | - Yue Lian
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
| | - Yi-Xuan Yang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Wei Wei
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
| | - Tao Liu
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
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Aardoom MA, Klomberg RCW, Kemos P, Ruemmele FM, van Ommen CH(H, de Ridder L, Croft NM. The Incidence and Characteristics of Venous Thromboembolisms in Paediatric-Onset Inflammatory Bowel Disease: A Prospective International Cohort Study Based on the PIBD-SETQuality Safety Registry. J Crohns Colitis 2022; 16:695-707. [PMID: 34599822 PMCID: PMC9228884 DOI: 10.1093/ecco-jcc/jjab171] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS Guidelines regarding thromboprophylaxis for venous thromboembolisms [VTEs] in children with inflammatory bowel disease [IBD] are based on limited paediatric evidence. We aimed to prospectively assess the incidence of VTEs in paediatric-onset IBD [PIBD], characterize PIBD patients with a VTE and identify potential IBD-related risk factors. METHODS From October 2016 to September 2020, paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD. IBD details [type, Paris classification, clinical and biochemical disease activity, treatment] and VTE details [type, location, treatment, outcome] were collected. To estimate VTE incidence, participants annually reported the number of PIBD patients, data source and catchment area of their centre. A systematic literature review and meta-analysis was performed to calculate the VTE incidence in the general paediatric population. RESULTS Participation of 129 PIBD centres resulted in coverage of 24 802 PIBD patients. Twenty cases of VTE were identified [30% Crohn's disease]. The incidence of VTEs was 3.72 (95% confidence interval [CI] 2.27-5.74) per 10 000 person-years, 14-fold higher than in the general paediatric population (0.27 [95% CI 0.18-0.38], p < 0.001). Cerebral sinus venous thrombosis was most frequently reported [50%]. All but one patient had active IBD, 45% were using steroids and 45% were hospitalized. No patient received thromboprophylaxis, whereas according to current PIBD guidelines, this was recommended in 4/20 patients. CONCLUSION There is an increased risk of VTEs in the PIBD population compared to the general paediatric population. Awareness of VTE occurrence and prevention should be extended to all PIBD patients with active disease, especially those hospitalized.
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Affiliation(s)
- Martine A Aardoom
- Department of Paediatric Gastroenterology, Erasmus Medical Centre – Sophia Children’s Hospital, Rotterdam, The Netherlands
| | - Renz C W Klomberg
- Department of Paediatric Gastroenterology, Erasmus Medical Centre – Sophia Children’s Hospital, Rotterdam, The Netherlands
| | - Polychronis Kemos
- Paediatric Gastroenterology, Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK
| | - Frank M Ruemmele
- Department of Paediatric Gastroenterology, Université Paris Descartes, Sorbonne Paris Cité, APHP, Hôpital Necker Enfants Malades, Paris, France
| | - C H (Heleen) van Ommen
- Department of Paediatric Haematology, Erasmus Medical Centre – Sophia Children’s Hospital, Rotterdam, the Netherlands
| | - Lissy de Ridder
- Department of Paediatric Gastroenterology, Erasmus Medical Centre – Sophia Children’s Hospital, Rotterdam, The Netherlands
| | - Nicholas M Croft
- Paediatric Gastroenterology, Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK
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Dang AK, Gonzalez DA, Kumar R, Asif S, Bali A, Anne KK, Konanur Srinivasa NK. Vinculum of Cardiovascular Disease and Inflammatory Bowel Disease: A Narrative Review. Cureus 2022; 14:e26144. [PMID: 35891823 PMCID: PMC9303831 DOI: 10.7759/cureus.26144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2022] [Indexed: 11/24/2022] Open
Abstract
Inflammatory bowel disease (IBD), comprising of ulcerative colitis (UC) and Crohn's disease (CrD), is a chronic relapsing-remitting inflammation of the bowel with extraintestinal involvement. Numerous studies published in the last decade have underlined the dangerous cardiovascular disease (CVD) outcomes of IBD, such as ischemic heart disease, heart failure, and stroke, and the need for better therapeutic and prognostic strategies. This article elucidated the pathological web of mechanisms that link IBD with CVD, such as immune dysregulation, endothelial dysfunction, arterial stiffness, and dysbiosis, with a comprehensive review of clinical studies standing for and against the notion in pediatric and adult populations. The current treatment and prevention aim at disease remission and dietary strategies shown to reduce the CVD risk. Exploration of other supplemental preventive and treatment methods, especially during active flares of disease, to reduce the risk of arterial thromboembolic disease (ATED) is the need of the hour.
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Rohani P, Taraghikhah N, Nasehi MM, Alimadadi H, Assadzadeh Aghdaei H. Cerebrovascular Events in Pediatric Inflammatory Bowel Disease: A Review of Published Cases. Pediatr Gastroenterol Hepatol Nutr 2022; 25:180-193. [PMID: 35611378 PMCID: PMC9110847 DOI: 10.5223/pghn.2022.25.3.180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 02/27/2022] [Accepted: 03/07/2022] [Indexed: 11/14/2022] Open
Abstract
Pediatric inflammatory bowel disease (PIBD) is a multisystem disorder characterized by intestinal and extraintestinal manifestations and complications. Cerebrovascular events (CVE) are rare extraintestinal complications in patients with PIBD. Statistics show that 3.3% patients with PIBD and 1.3-6.4% adult patients with inflammatory bowel disease (IBD) experience CVE during the course of the disease. Therefore, this study aimed to review the records of children with IBD who developed CVE during the course of the disease. We retrospectively reviewed 62 cases of PIBD complicated by CVE. The mean patient age at the time of thrombotic events was 12.48±4.13 years. The incidence of ulcerative colitis was significantly higher than that of Crohn's disease (43 [70.5%] vs. 13 [21.3%] patients). Most patients (87.93%) were in the active phase of IBD at the time of CVE. The mean time interval between the onset of IBD and CVE was 20.84 weeks. Overall, 11 (26.83%) patients showed neurological symptoms of CVE at disease onset. The most frequent symptom on admission was persistent and severe headaches (67.85%). The most common site of cerebral venous thrombosis was the transverse sinuses (n=23, 53.48%). The right middle cerebral artery (n=3, 33.34%) was the predominant site of cerebral arterial infarction. Overall, 41 (69.49%) patients who were mostly administered unfractionated heparin or low-molecular-weight heparin (56.09%) recovered completely. Patients with IBD are at a risk of thromboembolism. CVE may be the most common type of thromboembolism. Based on these findings, the most common risk factor for CVE is IBD flares. In patients with CVE, anticoagulant therapy with heparin, followed by warfarin, is necessary.
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Affiliation(s)
- Pejman Rohani
- Pediatric Gastroenterology and Hepatology Research Center, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
| | - Nazanin Taraghikhah
- Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Mehdi Nasehi
- Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences, Research Institute for Children Health, Tehran, Iran
| | - Hosein Alimadadi
- Pediatric Gastroenterology and Hepatology Research Center, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Assadzadeh Aghdaei
- Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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7
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Deshpande GG, Riffle RM, Meagher S. Basilar artery stroke in Crohn's disease treated with endovascular thromboembolectomy. BMJ Case Rep 2022; 15:e244652. [PMID: 35410945 PMCID: PMC9003607 DOI: 10.1136/bcr-2021-244652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2021] [Indexed: 11/04/2022] Open
Abstract
We describe a girl in middle childhood with newly diagnosed Crohn's disease, who presented with seizures and altered mental status. MRI showed an abnormal vascular signal at the basilar artery, but no evidence of acute ischaemia. Her weakness worsened over the next 8 hours to dense quadriplegia. CT angiography of the brain, approximately 24 hours after the initial onset of symptoms, identified an acute basilar artery occlusion with infarction. She received endovascular thromboembolectomy emergently. She showed significant improvement over 8-month period from quadriplegia to walking unassisted. This case highlights the importance of recognising stroke in patients with inflammatory bowel disease and the need for emergent radiological assessment and potential intervention.
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Affiliation(s)
- Girish G Deshpande
- Department of Pediatrics, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA
| | - Riana M Riffle
- Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Sean Meagher
- Radiology and Neurological Surgery, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA
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De Laffolie J, Ballauff A, Wirth S, Blueml C, Rommel FR, Claßen M, Laaß M, Lang T, Hauer AC. Occurrence of Thromboembolism in Paediatric Patients With Inflammatory Bowel Disease: Data From the CEDATA-GPGE Registry. Front Pediatr 2022; 10:883183. [PMID: 35722497 PMCID: PMC9204097 DOI: 10.3389/fped.2022.883183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/14/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Among patients with inflammatory bowel disease (IBD), the risk of thromboembolism (TE) is increased, representing a relevant cause of morbidity and mortality. In contrast to other extraintestinal IBD manifestations, TE receives much less attention because of its low incidence, estimated at merely 0.4-0.9% in hospitalised children with IBD. METHODS Cases with TE, as documented in the German-Austrian Paediatric IBD registry gesellschaft für pädiatrische gastroenterologie und ernährung - large paediatric patient registry (CEDATA-GPGE), were analyzed retrospectively. For all patients with signs of TE, a questionnaire was filled in by the treating paediatric gastroenterologist. RESULTS Over 10 years, 4,153 paediatric patients with IBD (0-18 years) were registered in the registry, and 12 of them identified with TE. Eight patients were diagnosed with ulcerative colitis (UC), three with Crohn's disease (CD), and one with IBD-unclassified. The median age at IBD diagnosis was 10 years and at the manifestation of TE 13 years, respectively, with a median latency to TE of 2 years. Prevalence of TE was 0.3%, with a significantly higher risk for patients with UC than CD (OR 5.9, CI 1.56-22.33, p = 0.008). More girls than boys were affected (f:m = 7:5) without reaching significance. Approximately 90% of patients experienced TE during active disease, with relevant cerebral and limb involvement in 6/12 patients. Various risk factors, e.g., hospitalisation, coagulopathy, or anaemia were identified. TE management included intensive care and surgery. Among the 12 patients, 11 recovered fully, in which one patient has focal epilepsy as a sequela. CONCLUSION Paediatric patients with IBD have a substantially increased risk for TE. Risk factors, such as those identified should be considered when managing paediatric IBD and preventive measures for those hospitalised taken routinely. Initiating pharmacological thromboprophylaxis is challenging for the lack of published trials on efficacy and safety in paediatric IBD but should be considered carefully in each case.
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Affiliation(s)
- Jan De Laffolie
- Department of General Pediatrics and Neonatology, University of Giessen, Giessen, Germany
| | | | - Stefan Wirth
- Kinderklinik, Helios Klinikum Wuppertal, Wuppertal, Germany
| | - Carolin Blueml
- Department of Paediatrics, Philipps-University Marburg, Marburg, Germany
| | - Frank Risto Rommel
- Department of General Pediatrics and Neonatology, University of Giessen, Giessen, Germany
| | | | - Martin Laaß
- Children's Hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Thomas Lang
- Kinderklinik Regensburg, Regensburg, Germany
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Ferro JM, Oliveira Santos M. Neurology of inflammatory bowel disease. J Neurol Sci 2021; 424:117426. [PMID: 33810878 DOI: 10.1016/j.jns.2021.117426] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/21/2020] [Accepted: 03/24/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel diseases (IBD) are chronic inflammatory conditions affecting the digestive system, comprising two main distinctive entities, ulcerative colitis (UC) and Crohn's disease (CD). Besides gastrointestinal manifestations, IBD causes extraintestinal manifestations in the central and peripheral nervous system. The incidence of neurological complications in IBD ranges from 0.25% to 47.5%. The pathophysiology of neurological manifestations of IBD is mostly immune mediated, but dysfunction of the brain-gut axis, arterial and venous thromboembolism, infections, nutritional deficiencies and side-effects of medications (steroids, metronidazole, sulfasalazine, anti-TNF-α, anti-integrin antibodies) are other contributory mechanisms. Patients with IBD have an increased risk of arterial and venous stroke, mainly during periods of exacerbations. Vasculitis is extremely rare. There is a bidirectional association between multiple sclerosis and IBD, with a relative risk for comorbidity of 1.54, being 1.53 for the risk of multiple sclerosis in IBD and 1.55 for the risk of IBD in multiple sclerosis patients. Anti-TNF-α therapy is contraindicated in the treatment of patients who have both IBD and multiple sclerosis. Demyelinating disorders can also be a rare complication of anti-TNF-α therapy. Optic neuritis, transverse myelitis, progressive myelopathy, central nervous system infections, epilepsy and encephalopathy are among other uncommon neurological complications. Peripheral nervous system manifestations include peripheral neuropathy, either demyelination and axonal, myasthenia gravis and polymyositis/dermatomyositis and localized forms of myositis.
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Affiliation(s)
- José M Ferro
- Serviço de Neurologia, Department of Neurological Sciences and Mental Health, Hospital de Santa Maria - CHULN, Lisboa, Portugal; Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal.
| | - Miguel Oliveira Santos
- Serviço de Neurologia, Department of Neurological Sciences and Mental Health, Hospital de Santa Maria - CHULN, Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal
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10
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The risk of cardiovascular complications in inflammatory bowel disease. Clin Exp Med 2020; 20:481-491. [PMID: 32785793 PMCID: PMC7568702 DOI: 10.1007/s10238-020-00639-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 06/15/2020] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing disease of unknown etiology involving gastrointestinal tract. IBD comprises two main entities: ulcerative colitis and Crohn's disease. Several studies showed increased risk of cardiovascular complications in chronic inflammatory disorders, especially during IBD relapses. Endothelium plays a role in physiologic regulation of vascular tone, cell adhesion, migration and resistance to thrombosis. Also, its dysfunction is associated with increased risk of atherosclerosis development. There are several potential links between chronic IBD-related inflammatory processes and the risk of cardiovascular disease, but insight into pathogenetic pathways remains unclear. We present the current concepts and review of adult and pediatric studies on the risk of CVD in IBD.
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Epidemiologische Forschung und Behandlungsdatenanalyse zu chronisch-entzündlichen Darmerkrankungen. Monatsschr Kinderheilkd 2020. [DOI: 10.1007/s00112-020-00852-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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12
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Turner D, Ruemmele FM, Orlanski-Meyer E, Griffiths AM, de Carpi JM, Bronsky J, Veres G, Aloi M, Strisciuglio C, Braegger CP, Assa A, Romano C, Hussey S, Stanton M, Pakarinen M, de Ridder L, Katsanos KH, Croft N, Navas-López VM, Wilson DC, Lawrence S, Russell RK. Management of Paediatric Ulcerative Colitis, Part 2: Acute Severe Colitis-An Evidence-based Consensus Guideline From the European Crohn's and Colitis Organization and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 67:292-310. [PMID: 30044358 DOI: 10.1097/mpg.0000000000002036] [Citation(s) in RCA: 153] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Acute severe colitis (ASC) is one of the few emergencies in pediatric gastroenterology. Tight monitoring and timely medical and surgical interventions may improve outcomes and minimize morbidity and mortality. We aimed to standardize daily treatment of ASC in children through detailed recommendations and practice points which are based on a systematic review of the literature and consensus of experts. METHODS These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Fifteen predefined questions were addressed by working subgroups. An iterative consensus process, including 2 face-to-face meetings, was followed by voting of the national representatives of ECCO and all members of the Paediatric Inflammatory Bowel Disease (IBD) Porto group of ESPGHAN (43 voting experts). RESULTS A total of 24 recommendations and 43 practice points were endorsed with a consensus rate of at least 91% regarding diagnosis, monitoring, and management of ASC in children. A summary flowchart is presented based on daily scoring of the Paediatric Ulcerative Colitis Activity Index. Several topics have been altered since the previous 2011 guidelines and from those published in adults. DISCUSSION These guidelines standardize the management of ASC in children in an attempt to optimize outcomes of this intensive clinical scenario.
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Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Frank M Ruemmele
- Université Paris Descartes, Sorbonne Paris Cité, APHP, Hôpital Necker Enfants Malades, Paris, France
| | | | - Anne M Griffiths
- The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | | | - Jiri Bronsky
- Department of Paediatrics, University Hospital Motol, Prague, Czech Republic
| | - Gabor Veres
- Ist Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialistic Surgery, University of Campania "Luigi Vanvitelli," Napoli, Italy
| | | | - Amit Assa
- Schneider Children's Hospital, Petach Tikva (affiliated to the Sackler Faculty of Medicine), Tel Aviv University, Tel Aviv, Israel
| | - Claudio Romano
- Pediatric Department, University of Messina, Messina, Italy
| | - Séamus Hussey
- National Children's Research Centre, Royal College of Surgeons of Ireland and University College Dublin, Ireland
| | | | - Mikko Pakarinen
- Helsinki University Children's Hospital, Department of Pediatric Surgery, Helsinki, Finland
| | - Lissy de Ridder
- Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | | | - Nick Croft
- Barts and the London School of Medicine, Queen Mary University of London, London, UK
| | | | - David C Wilson
- Child Life and Health, University of Edinburgh, Edinburgh, UK
| | - Sally Lawrence
- BC Children's Hospital, University of British Columbia, Vancouver BC, Canada
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13
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Sigall-Boneh R, Levine A, Lomer M, Wierdsma N, Allan P, Fiorino G, Gatti S, Jonkers D, Kierkus J, Katsanos KH, Melgar S, Yuksel ES, Whelan K, Wine E, Gerasimidis K. Research Gaps in Diet and Nutrition in Inflammatory Bowel Disease. A Topical Review by D-ECCO Working Group [Dietitians of ECCO]. J Crohns Colitis 2017; 11:1407-1419. [PMID: 28961811 DOI: 10.1093/ecco-jcc/jjx109] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Accepted: 08/04/2017] [Indexed: 02/06/2023]
Abstract
Although the current doctrine of IBD pathogenesis proposes an interaction between environmental factors and gut microbiota in genetically susceptible individuals, dietary exposures have attracted recent interest and are, at least in part, likely to explain the rapid rise in disease incidence and prevalence. The D-ECCO working group along with other ECCO experts with expertise in nutrition, microbiology, physiology, and medicine reviewed the evidence investigating the role of diet and nutritional therapy in the onset, perpetuation, and management of IBD. A narrative topical review is presented where evidence pertinent to the topic is summarised collectively under three main thematic domains: i] the role of diet as an environmental factor in IBD aetiology; ii] the role of diet as induction and maintenance therapy in IBD; and iii] assessment of nutritional status and supportive nutritional therapy in IBD. A summary of research gaps for each of these thematic domains is proposed, which is anticipated to be agenda-setting for future research in the area of diet and nutrition in IBD.
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Affiliation(s)
- Rotem Sigall-Boneh
- PIBD Research Center, Pediatric Gastroenterology and Nutrition Unit, Edith Wolfson Medical Center, Israel
| | - Arie Levine
- Paediatric Gastroenterology & Nutrition Unit, Wolfson Medical Center, Tel Aviv University, Israel
| | - Miranda Lomer
- Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust and King's College London, UK
| | - Nicolette Wierdsma
- Department of Nutrition and Dietetics, VU University Medical Centre, The Netherlands
| | - Philip Allan
- Department of Translational Gastroenterology, John Radcliffe Hospital, UK
| | - Gionata Fiorino
- Department of Gastroenterology, IBD Center, Humanitas Research Hospital, Italy
| | - Simona Gatti
- Department of Paediatrics, Polytechnic University of Marche, Italy
| | - Daisy Jonkers
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, The Netherlands
| | - Jaroslaw Kierkus
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Children's Memorial Health Institute, Poland
| | - Konstantinos H Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Greece
| | - Silvia Melgar
- APC Microbiome Institute, University College Cork, Ireland
| | - Elif Saritas Yuksel
- Department of Gastroenterology, Izmir Katip Celebi University Ataturk Teaching and Research Hospital, Turkey
| | - Kevin Whelan
- King's College London, Division of Diabetes and Nutritional Sciences, UK
| | - Eytan Wine
- Division of Paediatric Gastroenterology and Nutrition, Departments of Paediatrics and Physiology, University of Alberta, Canada
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Abstract
There is a growing interest in the extraintestinal manifestations of common pediatric gastrointestinal diseases, such as inflammatory bowel disease and celiac disease. This article specifically focuses on the neurological symptoms that manifest because of these disorders and their treatments. Many neurological symptoms have been reported in association with these diseases, including neuropathy, myopathy, ataxia, headache, and seizures, among others. It is currently believed that these neurological symptoms are largely overlooked by practitioners and could be a red flag for earlier diagnosis. However, additional research, especially in the pediatric population, is warranted to further elaborate on the causality and pathophysiology of these neurological symptoms.
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Affiliation(s)
- Melissa Shapiro
- From the Section of Gastroenterology, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA
| | - David A Blanco
- From the Section of Gastroenterology, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA.
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Baumer FM, Ouahed J, Verhave M, Rivkin MJ. Fatal Central Nervous System Disease Following First Infliximab Infusion in a Child With Inflammatory Bowel Disease. Pediatr Neurol 2016; 57:91-4. [PMID: 26831951 DOI: 10.1016/j.pediatrneurol.2015.12.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 12/18/2015] [Accepted: 12/20/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND Infliximab is used in the treatment of inflammatory bowel disease. Previously reported neurological complications include central and peripheral demyelinating disorders and neuropathies occurring months into therapy. PATIENT DESCRIPTION A seven-year-old boy diagnosed with ulcerative colitis and primary sclerosing cholangitis received infliximab. Six hours following his uneventful infusion, he awoke with headache and emesis and rapidly became obtunded. Neurological examination revealed minimally reactive pupils and otherwise absent brainstem reflexes. Cranial computed tomography revealed hypodense lesions in the cerebral hemispheres, cerebellum, and pons accompanied by hemorrhage. Magnetic resonance imaging showed diffusion restriction concerning for ischemia with areas of ring enhancement suggestive of inflammation. Vessel imaging was normal, and cerebrospinal fluid and serum studies showed only an extremely elevated level of d-dimer. Echocardiogram showed depressed ventricular function but neither intracardiac shunt nor thrombus. Within four days he met criteria for brain death. Autopsy was refused. CONCLUSIONS This is the first report of a fulminant, fatal central nervous system process to occur after an initial dose of infliximab. The differential diagnosis includes multifocal arterial strokes and a devastating demyelinating process.
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Affiliation(s)
- Fiona M Baumer
- Department of Neurology, Boston Children's Hospital, Boston, Massachusetts.
| | - Jodie Ouahed
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts
| | - Menno Verhave
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts
| | - Michael J Rivkin
- Department of Neurology, Boston Children's Hospital, Boston, Massachusetts; Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts; Department of Radiology, Boston Children's Hospital, Boston, Massachusetts
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16
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Dolapcioglu C, Dolapcioglu H. Structural brain lesions in inflammatory bowel disease. World J Gastrointest Pathophysiol 2015; 6:124-130. [PMID: 26600970 PMCID: PMC4644876 DOI: 10.4291/wjgp.v6.i4.124] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 07/07/2015] [Accepted: 09/07/2015] [Indexed: 02/07/2023] Open
Abstract
Central nervous system (CNS) complications or manifestations of inflammatory bowel disease deserve particular attention because symptomatic conditions can require early diagnosis and treatment, whereas unexplained manifestations might be linked with pathogenic mechanisms. This review focuses on both symptomatic and asymptomatic brain lesions detectable on imaging studies, as well as their frequency and potential mechanisms. A direct causal relationship between inflammatory bowel disease (IBD) and asymptomatic structural brain changes has not been demonstrated, but several possible explanations, including vasculitis, thromboembolism and malnutrition, have been proposed. IBD is associated with a tendency for thromboembolisms; therefore, cerebrovascular thromboembolism represents the most frequent and grave CNS complication. Vasculitis, demyelinating conditions and CNS infections are among the other CNS manifestations of the disease. Biological agents also represent a risk factor, particularly for demyelination. Identification of the nature and potential mechanisms of brain lesions detectable on imaging studies would shed further light on the disease process and could improve patient care through early diagnosis and treatment.
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17
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Karmiris K, Bossuyt P, Sorrentino D, Moreels T, Scarcelli A, Legido J, Dotan I, Naismith GD, Jussila A, Preiss JC, Kruis W, Li ACY, Bouguen G, Yanai H, Steinwurz F, Katsanos KH, Subramaniam K, Tarabar D, Zaganas IV, Ben-Horin S. Cerebrovascular events in inflammatory bowel disease patients treated with anti-tumour necrosis factor alpha agents. J Crohns Colitis 2015; 9:382-9. [PMID: 25740813 DOI: 10.1093/ecco-jcc/jjv042] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Cerebrovascular accidents [CVA] have rarely been reported in inflammatory bowel disease [IBD] patients treated with anti-tumour necrosis alpha [anti-TNF alpha] agents. Our aim here was to describe the clinical course of CVA in these patients. METHODS This was a European Crohn's and Colitis Organisation [ECCO] retrospective observational study, performed as part of the CONFER [COllaborative Network For Exceptionally Rare case reports] project. A call to all ECCO members was made to report on IBD patients afflicted with CVA during treatment with anti-TNF alpha agents. Clinical data were recorded in a standardised case report form and analysed for event association with anti-TNF alpha treatment. RESULTS A total of 19 patients were identified from 16 centres: 14 had Crohn's disease, four ulcerative colitis and one IBD colitis unclassified [median age at diagnosis: 38.0 years, range: 18.6-62.5]. Patients received anti-TNF alpha for a median duration of 11.8 months [range: 0-62] at CVA onset; seven had previously been treated with at least one other anti-TNF alpha agent. Complete neurological recovery was observed in 16 patients. Anti-TNF alpha was discontinued in 16/19 patients. However, recurrent CVA or neurological deterioration was not observed in any of the 11 patients who received anti-TNF alpha after CVA [eight resumed after temporary cessation, three continued without interruption] for a median follow-up of 39.8 months [range: 5.6-98.2]. CONCLUSION These preliminary findings do not unequivocally indicate a causal role of anti-TNF alpha in CVA complicating IBD. Resuming or continuing anti-TNF alpha in IBD patients with CVA may be feasible and safe in selected cases, but careful weighing of IBD activity versus neurological status is prudent.
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Affiliation(s)
- Konstantinos Karmiris
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Crete, Greece
| | - Peter Bossuyt
- Imelda GI Clinical Research Center, Bonheiden, Belgium
| | - Dario Sorrentino
- IBD Center, Virginia Tech-Carilion School of Medicine, Roanoke, VA, USA and Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy
| | - Tom Moreels
- Department of Hepato-gastroenterology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Antonella Scarcelli
- Department of Gastroenterology, Azienda University Hospital, Policlinico di Modena, Italy
| | - Jesus Legido
- Gastroenterology Unit, Segovia General Hospital, Segovia, Spain
| | - Iris Dotan
- IBD Center, Department of Gastroenterology and Liver Diseases and the Sackler School of Medicine, Sourasky Medical Center, Tel Aviv, Israel
| | | | - Airi Jussila
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | | | | | - Andy C Y Li
- Department of Gastroenterology, Western Sussex Hospitals NHSFT, Worthing, UK
| | - Guillaume Bouguen
- Department of Gastroenterology, University Hospital Pontchaillou, Rennes, France
| | - Henit Yanai
- Gastroenterology Unit, Segovia General Hospital, Segovia, Spain
| | | | | | - Kavitha Subramaniam
- Gastroenterology and Hepatology Unit, Canberra Hospital, Canberra, Australia
| | - Dino Tarabar
- Department of Gastroenterology, MMA Belgrade, Serbia
| | - Ioannis V Zaganas
- Department of Neurology, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical Center, Tel-Aviv University, Tel-Aviv, Israel
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18
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Abstract
Hepatic and gastrointestinal disorders can produce a wide spectrum of neurologic complications both affecting the central nervous system (CNS) and the peripheral nervous system. These manifestations range in severity from coma in acute liver failure and acute pancreatitis, to minor cognitive changes in chronic portosystemic encephalopathy and hepatitis C. Cerebrovascular diseases can complicate hepatitis C infection and inflammatory bowel disease. Demyelinating disorders may co-exist with inflammatory bowel disease. Anti-tumor necrosis factor alpha drugs may induce demyelination. Ataxia may occur in malabsorption syndromes and in gluten related disorders. Characteristic movement disorders are key features of acquired hepatocerebral degeneration and of Whipple disease. Multiple types of neuropathy can be found in association with hepatitis, inflammatory bowel disease and gluten related disorders.
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Affiliation(s)
- José M Ferro
- Department of Neurosciences, Service of Neurology, Hospital de Santa Maria, University of Lisbon, Av. Prof. Egas Moniz, 1649-035, Lisboa, Portugal,
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19
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Abstract
BACKGROUND Growing evidence has shown that coagulation processes play an important role in disease pathogenesis and/or disease progression in patients with inflammatory bowel disease. However, no study has ever focused on the possible influence of infliximab (IFX) therapy on the coagulation status in patients with Crohn's disease (CD). OBJECTIVE To investigate the difference in the coagulation biomarkers between the CD patients and the control participants, and evaluate the impact of IFX usage on the coagulation status of CD patients. PATIENTS AND METHODS A retrospective study that included a case-control study and a self-control study was designed. The medical records of CD patients and control participants were evaluated according to the inclusion and exclusion criteria. The results of laboratory tests including blood routine, coagulation, D-dimer, C-reactive protein, and erythrocyte sedimentation rate were retrieved to assess the coagulation state. RESULTS In the case-control study, almost all the parameters showed a statistically significant difference between the CD patients and the control participants, except for activated partial thromboplastin time and thrombin time (the P value ranged from 0.000 to 0.002). Most of the values of the parameters reverted to normal over time during IFX therapy in the self-control study. Moreover, the fibrinogen concentration decreased obviously after IFX infusion (P=0.000) and the D-dimer concentration also decreased obviously by about half of the start value after IFX usage (P=0.018). CONCLUSION IFX therapy could ameliorate the hypercoagulable state in patients with CD.
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21
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Abstract
Inflammatory bowel diseases (IBD) are chronic, relapsing and remitting inflammatory conditions affecting the digestive system, comprising two main distinctive diseases, ulcerative colitis (UC) and Crohn's disease (CD). Besides the classic gastrointestinal manifestations, a variable number of IBD patients present with extraintestinal manifestations, including central and peripheral nervous system involvement. Peripheral neuropathy is one of the most common complications. An inflammatory myopathy has also been found. Cranial neuropathies include the Melkersson-Rosenthal syndrome, optic neuritis, and sensorineural hearing loss. Patients with IBD have a remarkable thromboembolic tendency and are at increased risk of both venous and arterial thrombotic complications. The prothrombotic state in IBD has multiple contributors. Ischemic stroke occurs through several mechanisms, including large artery disease, small vessel disease, paradoxical embolism, endocarditis, vasculitis, and associated with anti-TNF-α therapy. Thrombosis of the dural sinus and cerebral veins are at least as frequent as arterial stroke in IBD. Multiple sclerosis has been repeatedly associated with IBD. Up to 50% of IBD present asymptomatic white matter lesions. Other central nervous system complications include a slowly progressive myelopathy, epidural and subdural spinal empyema secondary to fistulous extension from the rectum, seizures, and encephalopathy.
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22
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Owczarek D, Cibor D, Głowacki MK, Rodacki T, Mach T. Inflammatory bowel disease: epidemiology, pathology and risk factors for hypercoagulability. World J Gastroenterol 2014; 20:53-63. [PMID: 24415858 PMCID: PMC3886032 DOI: 10.3748/wjg.v20.i1.53] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Revised: 11/19/2013] [Accepted: 12/05/2013] [Indexed: 02/06/2023] Open
Abstract
Hypercoagulability observed in patients with inflammatory bowel diseases (IBD) may lead to thromboembolic events (TE), which affect the venous and arterial systems alike and are an important factor in patients' morbidity and mortality. The risk of TE in IBD patients has been demonstrated to be approximately three-fold higher as compared to the general population. The pathogenesis of thrombosis in IBD patients is multifactorial and not fully explained. The most commonly listed factors include genetic and immune abnormalities, disequilibrium between procoagulant and anticoagulant factors, although recently, the role of endothelial damage as an IBD-triggering factor is underlined. Several studies report that the levels of some coagulation enzymes, including fibrinogen, factors V, VII, VIII, active factor XI, tissue factor, prothrombin fragment 1 + 2 and the thrombin-antithrombin complex, are altered in IBD patients. It has been demonstrated that there is a significant decrease of tissue plasminogen activator level, a marked increase of plasminogen activator inhibitor type 1 and thrombin-activable fibrinolysis inhibitor, a significantly lower level of antithrombin III and tissue factor pathway inhibitor. IBD patients have been also observed to produce an increased amount of various anticoagulant antibodies. Hyperhomocysteinemia, which is a potential risk factor for TE was also observed in some IBD patients. Further studies are necessary to assess the role of coagulation abnormalities in IBD etiology and to determine indications for thromboprophylactic treatment in patients at high risk of developing TE.
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23
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Katsanos AH, Kosmidou M, Giannopoulos S, Katsanos KH, Tsivgoulis G, Kyritsis AP, Tsianos EV. Cerebral arterial infarction in inflammatory bowel diseases. Eur J Intern Med 2014; 25:37-44. [PMID: 24028931 DOI: 10.1016/j.ejim.2013.08.702] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2013] [Revised: 08/14/2013] [Accepted: 08/16/2013] [Indexed: 02/06/2023]
Abstract
It has been estimated that up to 10% of hypercoagulable state manifestations in patients with inflammatory bowel disease (IBD) are ischemic strokes. The literature search through MEDLINE and EMBASE highlighted 33 case reports of IBD patients complicated with cerebral arterial infarction during the course of their disease. Most of these patients presented with either left or right sided hemiparesis on admission, while the most common site of arterial infarction was either the right or the left middle cerebral artery. Thrombocytosis and anemia were the most commonly observed potential risk factors for stroke in the laboratory analysis. Other coagulation abnormalities, hereditary thrombotic mutations, hyperhomocysteinemia, hyperlipidemia, structural cardiac abnormalities, endocarditis and cerebral artery vasculitis have also been reported in some of the cases that were reviewed. Even though many of these findings are commonly observed in IBD patients, literature data is still controversial about their causal relationship to ischemic stroke. Similarly, there is also lack of steady evidence and official guidelines for stroke management in both children and adults with IBD comorbidity. Finally, an algorithm based on both the American Heart Association and European Stroke Organization guidelines for stroke management and prevention in the general population, is presented as a reference point for the treatment of IBD patients who are complicated by an ischemic cerebral event.
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Affiliation(s)
| | - Maria Kosmidou
- 1st Division of Internal Medicine & Hepato-Gastroenterology Unit, University of Ioannina School of Medicine, Ioannina, Greece
| | | | - Konstantinos H Katsanos
- 1st Division of Internal Medicine & Hepato-Gastroenterology Unit, University of Ioannina School of Medicine, Ioannina, Greece
| | - Georgios Tsivgoulis
- 2nd Dept. of Neurology, Attikon Hospital, University of Athens, Athens, Greece; International Clinical Research Center, Department of Neurology, St. Anne's University Hospital in Brno, Czech Republic
| | | | - Epameinondas V Tsianos
- 1st Division of Internal Medicine & Hepato-Gastroenterology Unit, University of Ioannina School of Medicine, Ioannina, Greece
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24
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Papay P, Miehsler W, Tilg H, Petritsch W, Reinisch W, Mayer A, Haas T, Kaser A, Feichtenschlager T, Fuchssteiner H, Knoflach P, Vogelsang H, Platzer R, Tillinger W, Jaritz B, Schmid A, Blaha B, Dejaco C, Sobala A, Weltermann A, Eichinger S, Novacek G. Clinical presentation of venous thromboembolism in inflammatory bowel disease. J Crohns Colitis 2013; 7:723-9. [PMID: 23127785 DOI: 10.1016/j.crohns.2012.10.008] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Accepted: 10/13/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Patients with inflammatory bowel disease (IBD) are at increased risk of venous thromboembolism (VTE), but data on frequency, site of thrombosis and risk factors are limited. We sought to determine prevalence, incidence as well as location and clinical features of first VTE among IBD patients. METHODS We evaluated a cohort of 2811 IBD patients for a history of symptomatic, objectively confirmed first VTE, recruited from 14 referral centers. Patients with VTE before IBD diagnosis or cancer were excluded. Incidence rates were calculated based on person-years from IBD diagnosis to first VTE or end of follow-up, respectively. RESULTS 2784 patients (total observation time 24,778 person-years) were analyzed. Overall, of 157 IBD patients with a history of VTE, 142 (90.4%) had deep vein thrombosis (DVT) and/or pulmonary embolism (PE), whereas 15 (9.6%) had cerebral, portal, mesenteric, splenic or internal jugular vein thrombosis. The prevalence and incidence rate of all VTE was 5.6% and 6.3 per 1000 person years, respectively. Patients with VTE were older at IBD diagnosis than those without VTE (34.4±14.8years vs 32.1±14.4years, p=0.045), but did not differ regarding sex, underlying IBD and disease duration. 121 (77.1%) VTE were unprovoked, 122 (77.7%) occurred in outpatients and 78 (60.9%) in patients with active disease. Medication at first VTE included corticosteroids (42.3%), thiopurines (21.2%), and infliximab (0.7%). CONCLUSION VTE is frequent in IBD patients. Most of them are unprovoked and occur in outpatients. DVT and PE are most common and unusual sites of thrombosis are rare.
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Affiliation(s)
- Pavol Papay
- Department of Internal Medicine III, Medical University Vienna, Austria
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25
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Tan VP, Chung A, Yan BP, Gibson PR. Venous and arterial disease in inflammatory bowel disease. J Gastroenterol Hepatol 2013; 28:1095-113. [PMID: 23662785 DOI: 10.1111/jgh.12260] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/26/2013] [Indexed: 12/13/2022]
Abstract
Awareness is increasing that risk of venous thromboembolism and development of atherosclerosis is elevated in patients with some chronic inflammatory diseases. This review aimed to examine the risk of vascular disease in patients with inflammatory bowel disease (IBD) and to identify potential pathogenic mechanisms and therapeutic approaches. An extensive literature search was conducted using MEDLINE database, Cochrane Library and international conference abstracts for studies pertaining to venous and arterial thromboembolism in adult IBD patients. There is a 1.1-3.6 fold risk of venothromboembolism in IBD, affecting 0.55-6.15% of patients. Risks are increased during a flare or with chronically active inflammation. Evidence is building that there may be a modestly increased risk of arterial disease overall, despite evidence that traditional risk factors may be reduced. Multiple pathogenic factors have been identified including endothelial dysfunction, inflammation-mediated calcium deposition in the media of arteries, hyperhomocysteinemia, platelet activation, and altered coagulation and fibrinolysis. The key to active and preventive therapy is to effectively treat inflammation. Recommendations for prophylaxis of venothromboembolism have followed guidelines where they exist and have been extrapolated from studies of other at-risk conditions, as have those for arterial disease, where screening for risk factors and actively treating abnormalities is encouraged. In conclusion, patients with IBD are at considerably increased risk of venothromboembolism and probably of arterial disease, in particular mesenteric ischemia and ischemic heart disease. Increased penetration of gaps between this knowledge and clinical therapeutic action to prevent thromboembolic events into IBD clinical practice is needed.
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Affiliation(s)
- Victoria P Tan
- Department of Medicine, University of Hong Kong, Hong Kong SAR
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26
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Russell RK, Protheroe A, Roughton M, Croft NM, Murphy MS, Spray C, Rodrigues AF, Wilson DC, Puntis J, Cosgrove M, Tamok A, Rao P, Down C, Arnott IDR, Mitton SG. Contemporary outcomes for ulcerative colitis inpatients admitted to pediatric hospitals in the United Kingdom. Inflamm Bowel Dis 2013; 19:1434-40. [PMID: 23624885 DOI: 10.1097/mib.0b013e31828133d6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Pediatric ulcerative colitis (UC) care is variable with a lack of appropriate guidelines to guide practice until recently. METHODS UC inpatients <17 years old admitted to 23 U.K. pediatric hospitals had clinical details collected between September 2010 and 2011. Comparative data for 248 patients were available from a previous audit in 2008. RESULTS One hundred and seventy-six patients (98 males) of median age 13 years (interquartile range, 10-13) were analyzed; 23 were elective surgical admissions, 47 new diagnoses, and 106 needed acute medical care for established UC. Median length of stay was 6 days (interquartile range, 3-10) with no deaths. Eighty-eight of 126 patients (70%) with active disease had standard stool cultures performed (3 [2%] were positive), and 57 (45%) had Clostridium difficile toxin tested (none positive). Twenty-five of 66 (38%) emergency admissions had an abdominal x-ray on admission, and 13 of 66 patients (20%) had a Pediatric Ulcerative Colitis Activity Index score. There were 3 cases of toxic megacolon and 2 thromboses. Eighty-one of 116 patients (71%) responded to steroids. Nineteen patients who did not respond adequately to steroids received rescue therapy (7 infliximab, 11 ciclosporin, and 1 both) with overall response rate of 90%; 7 patients needed surgery acutely, 5 without previous rescue therapy. Compared with the 2008 data, stool culture rates improved significantly (86 of 121 [71%] versus 76 of 147 [52%], P = 0.001) as did heparinization rates (15 of 150 [10%] versus 5 of 215 [2%], P = 0.002) and rescue therapy usage (17 of 33 [52%] versus 10 of 38 [26%], P = 0.03). CONCLUSIONS There were signs of improving UC care with significantly increased rates of stool culture and rescue therapy. The majority of sites, however, did not use Pediatric Ulcerative Colitis Activity Index scores.
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Affiliation(s)
- Richard K Russell
- Department of Paediatric Gastroenterology, Yorkhill Hospital, Glasgow, United Kingdom.
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27
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Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations. J Pediatr Gastroenterol Nutr 2012; 55:93-108. [PMID: 22516861 PMCID: PMC3895471 DOI: 10.1097/mpg.0b013e31825959b8] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and subspecialty providers.
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Lazzerini M, Bramuzzo M, Maschio M, Martelossi S, Ventura A. Thromboembolism in pediatric inflammatory bowel disease: systematic review. Inflamm Bowel Dis 2011; 17:2174-83. [PMID: 21910180 DOI: 10.1002/ibd.21563] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2010] [Accepted: 10/08/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND Several studies suggest an increased risk of venous and arterial thromboembolism (TE) in adults with inflammatory bowel disease (IBD) compared to the general population. We performed a systematic review of studies on incidence and characteristic of TE in children with IBD. METHODS We searched Medline, LILACS, EMBASE, POPLINE, CINHAL, and reference lists of identified articles, without language restrictions, in August 2010. RESULTS Population studies suggest that there is an increased risk of TE in children with IBD compared to controls. TE occurred in children with IBD in all age ranges, mostly (82.8%) during active disease, and more frequently in children with ulcerative colitis (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.8-7.6). At least one specific risk factor for TE was recognized in 50% of cases; two risk factors were present in 24%. Out of 92 published cases of TE in children with IBD, 54.3% occurred in cerebral site, 26% in the limbs, 13% in the abdominal vessels, and the remaining in the retina and lungs. After a first episode of TE, an early recurrence was observed in 11.4% of children, a late recurrence in 10%. A number of different therapeutic schemes were used. Overall mortality was 5.7% and was mostly associated with cerebral TE. CONCLUSIONS Population studies are needed to clarify the risk of TE in children with IBD, the relative weight of other risk factors, the characteristics of the events, and to define guidelines of therapy and prophylaxis.
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Affiliation(s)
- Marzia Lazzerini
- Unit of Research on Health Services and International Health, Institute for Child Health IRCCS Burlo Garofolo, Trieste, Italy.
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Turner D, Travis SPL, Griffiths AM, Ruemmele FM, Levine A, Benchimol EI, Dubinsky M, Alex G, Baldassano RN, Langer JC, Shamberger R, Hyams JS, Cucchiara S, Bousvaros A, Escher JC, Markowitz J, Wilson DC, van Assche G, Russell RK, European Crohn's and Colitis Organization, Porto IBD Working Group, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN. Am J Gastroenterol 2011; 106:574-88. [PMID: 21224839 DOI: 10.1038/ajg.2010.481] [Citation(s) in RCA: 156] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Acute severe ulcerative colitis (ASC) is a potentially life-threatening disease. We aimed to formulate guidelines for managing ASC in children based on systematic review of the literature and robust consensus process. This manuscript is a product of a joint effort of the ECCO (European Crohn's and Colitis Organization), the Pediatric Porto Inflammatory Bowel Disease (IBD) Working group of ESPGHAN (European Society of Pediatric Gastroenterology, Hepatology, and Nutrition) and ESPGHAN. METHODS A group of 19 experts in pediatric IBD participated in an iterative consensus process including two face-to-face meetings. A total of 17 predefined questions were addressed by working subgroups based on a systematic review of the literature. RESULTS The recommendations and practice points were eventually endorsed with a consensus rate of at least 95% regarding: definitions, initial evaluation, standard therapy, timing of second-line therapy, the role of endoscopic evaluation and heparin prophylaxis, how to administer second-line medical therapy, how to assess response, surgical considerations, and discharge recommendations. A management flowchart is presented based on daily scoring of the Pediatric Ulcerative Colitis Activity Index (PUCAI), along with 28 formal recommendations and 34 practice points. CONCLUSIONS These guidelines provide clinically useful points to guide the management of ASC in children. Taken together, the recommendations offer a standardized protocol that allows effective monitoring of disease progress and timely treatment escalation when needed.
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Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
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Ogawa E, Sakakibara R, Yoshimatsu Y, Suzuki Y, Mouri T, Tateno F, Kishi M, Oda S, Imamura H. Crohn's disease and stroke in a young adult. Intern Med 2011; 50:2407-8. [PMID: 22001476 DOI: 10.2169/internalmedicine.50.5692] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 36-year-old man with a 21-year history of Crohn's disease suddenly developed left hemiparesis. He did not have atherosclerotic risk factors on admission, but he had marked dehydration which was likely due to prolonged home intravenous hyper-alimentation. Brain MRI revealed lacunar infarction in the right anterior corona radiata. An anticoagulation drug and a free-oxide scavenger successfully reversed his neurological deficits almost completely. Stroke in young adults less than 40 years old is extremely rare; therefore, we conclude that Crohn's disease can be a risk factor for acute ischemic stroke in our case, due most probably to dehydration and other complex mechanisms.
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Affiliation(s)
- Emina Ogawa
- Neurology, Internal Medicine, Sakura Medical Center, Toho University, Japan
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Van Limbergen J, Griffiths AM. Pediatric Inflammatory Bowel Disease in the Emergency Department. CLINICAL PEDIATRIC EMERGENCY MEDICINE 2010. [DOI: 10.1016/j.cpem.2010.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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