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Leitão AMF, Thomas FP, Souza MHLPD, Braga LLBC, Gondim FDAA. The prevalence of myasthenia gravis is increased in inflammatory bowel disease. ARQUIVOS DE NEURO-PSIQUIATRIA 2025; 83:1-9. [PMID: 40360002 DOI: 10.1055/s-0045-1807717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
Comorbid autoimmune disorders affect approximately 0.2% of the population. A second autoimmune disease occurs in up to 15% of myasthenia gravis (MG) patients.To evaluate the association between MG and inflammatory bowel disease (IBD).We conducted a cross-sectional study involving a Brazilian cohort of IBD patients and a literature review.In 2022, we found 1 MG patient with ulcerative colitis and 3 with Crohn's disease out of 606 IBD patients (0.66% prevalence). The patient with UC and MG died in April 2024. The mean IBD onset age was 33.5 ± 2.7; patients were 45.8 ± 7.3-years-old at evaluation. Further, 2 patients were acetylcholine receptor antibody positive, 1 was anti-muscle specific kinase positive, and 1 seronegative. Also, 3 had abnormal repetitive nerve stimulation, all had normal nerve conduction studies, abnormal skin wrinkling test, and mild small fiber neuropathy. None had thymoma and/or underwent thymectomy. According to the MG Foundation's classification, one was class V, one IVb, and two IIa. The MG diagnosis was masked by immunotherapy in all. The prevalence ratio of MG in IBD patients versus the proportion of MG among all patients in our center was 8.56 (p < 0.0001, CI = 3.1-23.5). Considering the lowest and highest prevalence of this condition reported in the literature, the ratio is 44.0 (p < 0.0001, CI: 16.3-118.4) and 26.4 (p < 0.0001, CI: 9.8-70.6), respectively.The prevalence of MG is higher in IBD, may include muscle specific kinase positive disease (first report in the literature) and frequently overlaps with other autoimmune conditions and small fiber neuropathy.
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Affiliation(s)
| | - Florian P Thomas
- Hackensack University Medical Center, Hackensack Meridian School of Medicine, Department of Neurology, Hackensack NJ, United States
| | | | - Lúcia Libanez Bessa Campelo Braga
- Universidade Federal do Ceará, Faculdade de Medicina, Departamento de Medicina Clínica, Serviço de Gastroenterologia, Fortaleza CE, Brazil
| | - Francisco de Assis Aquino Gondim
- Universidade Federal do Ceará, Faculdade de Medicina, Departamento de Medicina Clínica, Serviço de Neurologia, Fortaleza CE, Brazil
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2
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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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Casey M, Pannu S, Bajwa S, Duarte-García A, Putman M. Risk of Neuroinflammatory Diseases Among New Recipients of Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs. Arthritis Care Res (Hoboken) 2024; 76:1203-1209. [PMID: 38570894 DOI: 10.1002/acr.25340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 02/15/2024] [Accepted: 03/29/2024] [Indexed: 04/05/2024]
Abstract
OBJECTIVE Neuroinflammatory adverse events have been observed among new users of tumor necrosis factor (TNF) inhibitors. No studies to date have compared the real-world risk of TNFs with other new users of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). The objective of this study is to describe the risk of neuroinflammatory disease after initiation b/tsDMARDs. METHODS This new user comparative effectiveness cohort study used a large US-based electronic health records database to describe the unadjusted incidence of neuroinflammatory adverse events over a 3-year period. The cohort included patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis initiating treatment with a TNF inhibitor (n = 93,661) or other b/tsDMARD (n = 38,354). RESULTS Among 132,015 patients included in the analysis, the most common first biologic agent was a TNF inhibitor; the unadjusted incidence of neuroinflammatory events was numerically lower among new users of TNF inhibitors (incidence 1.34 per 1,000 patient-years) as compared with the combined non-TNF group (1.69 per 1,000 patient-years). There was no significant association between TNF exposure and neuroinflammatory events as compared with the combined non-TNF b/tsDMARDs overall (hazard ratio 1.01; 95% confidence interval 0.75-1.36) and within each disease group. CONCLUSION The overall risk of neuroinflammatory events among new users of TNF inhibitors did not differ substantially as compared with new users of other b/tsDMARDs. Meta-analyses of randomized trials should be conducted to corroborate these findings, which may be affected by channeling bias.
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Affiliation(s)
| | - Sonia Pannu
- University School of Milwaukee, River Hills, Wisconsin
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Gordon H, Burisch J, Ellul P, Karmiris K, Katsanos K, Allocca M, Bamias G, Barreiro-de Acosta M, Braithwaite T, Greuter T, Harwood C, Juillerat P, Lobaton T, Müller-Ladner U, Noor N, Pellino G, Savarino E, Schramm C, Soriano A, Michael Stein J, Uzzan M, van Rheenen PF, Vavricka SR, Vecchi M, Zuily S, Kucharzik T. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2024; 18:1-37. [PMID: 37351850 DOI: 10.1093/ecco-jcc/jjad108] [Citation(s) in RCA: 74] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Indexed: 06/24/2023]
Affiliation(s)
- Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, London, Centre for Immunobiology, Blizard Institute, Faculty of Medicine, Barts & The London Medical School, Queen Mary University of London, UK
| | - Johan Burisch
- Gastrounit, medical division, Hvidovre Hospital, University of Copenhagen, Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | | | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Giorgos Bamias
- GI Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Manuel Barreiro-de Acosta
- University Hospital Santiago De Compostela CHUS, Department of Gastroenterology - IBD Unit, Santiago De Compostela, Spain
| | - Tasanee Braithwaite
- School of Immunology and Microbiology, King's College London, The Medical Eye Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK
| | - Thomas Greuter
- Division of Gastroenterology and Hepatology, GZO - Zurich Regional Health Center, Wetzikon, Division of Gastroenterology and Hepatology, University Hospital Lausanne - CHUV, Lausanne, Switzerland; Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Catherine Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Pascal Juillerat
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland; Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Triana Lobaton
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent; Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Ulf Müller-Ladner
- Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus Liebig University Giessen, Bad Nauheim, Germany
| | - Nurulamin Noor
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Gianluca Pellino
- Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB, Barcelona, Spain; Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Christoph Schramm
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alessandra Soriano
- Gastroenterology Division and IBD Center, Internal Medicine Department, Azienda Unità Sanitaria Locale - IRCCS, 42122 Reggio Emilia, Italy
| | - Jürgen Michael Stein
- Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Department of Gastroenterology and Clinical Nutrition, DGD Clinics Sachsenhausen, Frankfurt/Main, Germany
| | - Mathieu Uzzan
- Department of Gastroenterology, Hôpital Henri Mondor, APHP, Créteil, France
| | - Patrick F van Rheenen
- Department of Paediatric Gastroenterology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland
| | - Maurizio Vecchi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Stephane Zuily
- Vascular Medicine Division and French Referral Center for Rare Auto-Immune Diseases, Université de Lorraine, INSERM, DCAC and CHRU-Nancy, Nancy, France
| | - Torsten Kucharzik
- Department of Gastroenterology, Lüneburg Hospital, University of Münster, Lüneburg, Germany
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Joo H, Lee CS, Joe S, Han J, Kim HK, Cho H. Bickerstaff's brainstem encephalitis: a rare case of neurologic complication in Ulcerative Colitis. BMC Neurol 2023; 23:386. [PMID: 37884876 PMCID: PMC10601158 DOI: 10.1186/s12883-023-03430-0] [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] [Received: 06/26/2023] [Accepted: 10/07/2023] [Indexed: 10/28/2023] Open
Abstract
Bickerstaff's brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient's serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient's clinical course and history, he was diagnosed with Bickerstaff's brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis.
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Affiliation(s)
- Haram Joo
- Department of Neurology, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea
| | - Chung Seok Lee
- Department of Neurology, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea
| | - Sangwon Joe
- Department of Neurology, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea
| | - Jinu Han
- Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea
| | - Han-Kyeol Kim
- Department of Neurology, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea.
| | - Hanna Cho
- Department of Neurology, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea
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Hey GE, Vedam-Mai V, Beke M, Amaris M, Ramirez-Zamora A. The Interface between Inflammatory Bowel Disease, Neuroinflammation, and Neurological Disorders. Semin Neurol 2023; 43:572-582. [PMID: 37562450 DOI: 10.1055/s-0043-1771467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Abstract
Inflammatory Bowel Disease (IBD) is a complex, chronic inflammatory condition affecting the gastrointestinal tract. IBD has been associated with a variety of neurologic manifestations including peripheral nerve involvement, increased risk of thrombotic, demyelinating and events. Furthermore, an evolving association between IBD and neurodegenerative disorders has been recognized, and early data suggests an increased risk of these disorders in patients diagnosed with IBD. The relationship between intestinal inflammatory disease and neuroinflammation is complex, but the bidirectional interaction between the brain-gut-microbiome axis is likely to play an important role in the pathogenesis of these disorders. Identification of common mechanisms and pathways will be key to developing potential therapies. In this review, we discuss the evolving interface between IBD and neurological conditions, with a focus on clinical, mechanistic, and potentially therapeutic implications.
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Affiliation(s)
- Grace E Hey
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
| | - Vinata Vedam-Mai
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
| | - Matthew Beke
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
- Department of Food Science and Human Nutrition, University of Florida, Gainesville, Florida
| | - Manuel Amaris
- Department of Gastroenterology, University of Florida, Gainesville, Florida
| | - Adolfo Ramirez-Zamora
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
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Papadopoulou M, Tzortsou S, Chatzi I, Baltogiannis C. Oculomotor nerve palsy as an extraintestinal manifestation of Crohn's disease. BMJ Case Rep 2023; 16:e254456. [PMID: 37202111 PMCID: PMC10201219 DOI: 10.1136/bcr-2022-254456] [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: 05/05/2023] [Indexed: 05/20/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) may present with extraintestinal manifestations. Neurological symptoms associated with IBD are infrequent. Thus, any unexplained neurological symptom that occurs in patients with IBD should raise the suspicion of a link between the two disorders. We report a case of a man in his 60s, who was diagnosed with Crohn's disease and developed ptosis and diplopia. Neurological examination revealed oculomotor nerve palsy, sparing the pupil. MRI and magnetic resonance angiography of the brain were insignificant and no other cause was determined. He was treated with oral corticosteroids and symptoms gradually subsided. Cranial nerve palsies associated with IBD have been rarely reported. They usually involve the optic and acoustic nerve and are attributed to a common dysimmune base. This is the first reported case of oculomotor nerve palsy (III cranial nerve) associated with IBD. Clinicians treating patients with IBD should be alert for unusual neurological complications and treat them appropriately.
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Affiliation(s)
- Marianna Papadopoulou
- Department of Physiotherapy, University of West Attica, Egaleo, Greece
- Department of Neurology, Hygeias Melathron, Athens, Greece
| | - Sofia Tzortsou
- Department of Neurology, Hygeias Melathron, Athens, Greece
| | - Ioanna Chatzi
- Department of Neurology, Hygeias Melathron, Athens, Greece
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8
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Abu-Abaa M, Al-Qaysi G, Hassan A, Kananeh S. Subarachnoid Hemorrhage With Multifocal Cerebral Aneurysms in a Patient With Crohn’s Disease and Sjögren's Syndrome: A Case Report and Literature Review. Cureus 2023; 15:e35585. [PMID: 37007320 PMCID: PMC10063248 DOI: 10.7759/cureus.35585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2023] [Indexed: 03/04/2023] Open
Abstract
Only a few reports of the association between Crohn's disease (CD) and Sjögren's syndrome (SS) have been documented in the medical literature. Herein, we are presenting a 61-year-old female patient who presented with subarachnoid hemorrhage (SAH). She has a past medical history of primary SS on no active treatment, and CD in remission while on maintenance immunotherapy. She also tested positive for COVID-19. Computed tomography angiography (CTA) brain as well as cerebral angiogram revealed multifocal cerebral aneurysms. Successful coiling was achieved with a cerebral angiogram. This case serves to add to a limited body of reported cases and remind clinicians of the association between SS/CD and cerebral aneurysms. Herein, we review the literature regarding this association and also the effect of immunotherapy and COVID-19 on the progression of cerebral aneurysms.
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9
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Yang C, Fagan AM, Perrin RJ, Rhinn H, Harari O, Cruchaga C. Mendelian randomization and genetic colocalization infer the effects of the multi-tissue proteome on 211 complex disease-related phenotypes. Genome Med 2022; 14:140. [PMID: 36510323 PMCID: PMC9746220 DOI: 10.1186/s13073-022-01140-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 11/10/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Human proteins are widely used as drug targets. Integration of large-scale protein-level genome-wide association studies (GWAS) and disease-related GWAS has thus connected genetic variation to disease mechanisms via protein. Previous proteome-by-phenome-wide Mendelian randomization (MR) studies have been mainly focused on plasma proteomes. Previous MR studies using the brain proteome only reported protein effects on a set of pre-selected tissue-specific diseases. No studies, however, have used high-throughput proteomics from multiple tissues to perform MR on hundreds of phenotypes. METHODS Here, we performed MR and colocalization analysis using multi-tissue (cerebrospinal fluid (CSF), plasma, and brain from pre- and post-meta-analysis of several disease-focus cohorts including Alzheimer disease (AD)) protein quantitative trait loci (pQTLs) as instrumental variables to infer protein effects on 211 phenotypes, covering seven broad categories: biological traits, blood traits, cancer types, neurological diseases, other diseases, personality traits, and other risk factors. We first implemented these analyses with cis pQTLs, as cis pQTLs are known for being less prone to horizontal pleiotropy. Next, we included both cis and trans conditionally independent pQTLs that passed the genome-wide significance threshold keeping only variants associated with fewer than five proteins to minimize pleiotropic effects. We compared the tissue-specific protein effects on phenotypes across different categories. Finally, we integrated the MR-prioritized proteins with the druggable genome to identify new potential targets. RESULTS In the MR and colocalization analysis including study-wide significant cis pQTLs as instrumental variables, we identified 33 CSF, 13 plasma, and five brain proteins to be putative causal for 37, 18, and eight phenotypes, respectively. After expanding the instrumental variables by including genome-wide significant cis and trans pQTLs, we identified a total of 58 CSF, 32 plasma, and nine brain proteins associated with 58, 44, and 16 phenotypes, respectively. For those protein-phenotype associations that were found in more than one tissue, the directions of the associations for 13 (87%) pairs were consistent across tissues. As we were unable to use methods correcting for horizontal pleiotropy given most of the proteins were only associated with one valid instrumental variable after clumping, we found that the observations of protein-phenotype associations were consistent with a causal role or horizontal pleiotropy. Between 66.7 and 86.3% of the disease-causing proteins overlapped with the druggable genome. Finally, between one and three proteins, depending on the tissue, were connected with at least one drug compound for one phenotype from both DrugBank and ChEMBL databases. CONCLUSIONS Integrating multi-tissue pQTLs with MR and the druggable genome may open doors to pinpoint novel interventions for complex traits with no effective treatments, such as ovarian and lung cancers.
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Affiliation(s)
- Chengran Yang
- Department of Psychiatry, Washington University School of Medicine, 4444 Forest Park Ave., Box 8134, St. Louis, MO, 63108, USA
- NeuroGenomics and Informatics Center, Washington University School of Medicine, St Louis, MO, USA
- Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
| | - Anne M Fagan
- Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
- Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
- The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
| | - Richard J Perrin
- Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
- Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
- The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
| | - Herve Rhinn
- Department of Bioinformatics, Alector, Inc., 151 Oyster Point Blvd. #300, South San Francisco, CA, USA
| | - Oscar Harari
- Department of Psychiatry, Washington University School of Medicine, 4444 Forest Park Ave., Box 8134, St. Louis, MO, 63108, USA
- NeuroGenomics and Informatics Center, Washington University School of Medicine, St Louis, MO, USA
- Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
- The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
| | - Carlos Cruchaga
- Department of Psychiatry, Washington University School of Medicine, 4444 Forest Park Ave., Box 8134, St. Louis, MO, 63108, USA.
- NeuroGenomics and Informatics Center, Washington University School of Medicine, St Louis, MO, USA.
- Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA.
- The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
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Jayasundara JMHD, Samarawickrama VT, Peiris R, Aponso T, Abeynayake D. Concomitant Guillain-Barré Syndrome in a young Sri Lankan male with severe ulcerative colitis. BMC Gastroenterol 2022; 22:411. [PMID: 36064313 PMCID: PMC9444105 DOI: 10.1186/s12876-022-02455-y] [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: 08/21/2021] [Accepted: 07/20/2022] [Indexed: 11/25/2022] Open
Abstract
Background Guillain–Barré Syndrome is an immune mediated polyneuropathy. Ulcerative Colitis is an immune mediated chronic inflammatory condition mainly of the large intestine. Guillain–Barré Syndrome can present as a rare extraintestinal manifestation of Ulcerative Colitis when in remission or in a relapse. However, the concomitant presentation of Guillain–Barré Syndrome during a relapse of Ulcerative Colitis is very rare and only a few cases are reported to date. Case presentation A 24 year old young male diagnosed of Ulcerative Colitis presented with bloody diarrhea of frequency more than six times a day. He had been in clinical remission even after defaulting treatment for more than a year. He had also noted difficulty in walking prior to admission to the hospital. He was managed as for a severe relapse of Ulcerative Colitis and Guillain–Barré Syndrome. Appropriate management of both the illnesses helped him to recover. Conclusion Immune mediated diseases can have rare coexisting presentations. We report a case of Ulcerative Colitis with concomitant Guillain–Barré Syndrome. It is essential to be open minded and timely, appropriate treatment led to successful management of both the illnesses.
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Affiliation(s)
| | | | | | - Tilan Aponso
- National Hospital of Sri Lanka, Colombo, Sri Lanka
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11
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Yang Y, Zhang Y. Acute transverse myelitis in an adult-patient with underlying ulcerative colitis: a case report. BMC Gastroenterol 2022; 22:161. [PMID: 35365068 PMCID: PMC8973794 DOI: 10.1186/s12876-022-02230-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 03/22/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease that limits to colon mucosa, which characterised by relapsing and remitting abdominal pain and diarrhea. Neurological complications in UC patients are usually underestimated. The most frequently reported neurological disorders associated with UC are peripheral neuropathy, cerebrovascular disease and demyelinating disease. However, acute transverse myelitis (TM) is rarely reported in UC patients. CASE PRESENTATION We report a case of a 39-year-old man presented with fatigue, muscle weakness, numbness in the lower limbs and fingers with underlying UC. Laboratory results revealed elevated neutrophil count, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. Strip-shaped high signal intensity was identified in the cervical and thoracic spinal cord on T2-weighted magnetic resonance imaging. Acute TM was diagnosed. Significant improvements after intravenous high-dose methylprednisolone were observed. CONCLUSION We speculate that acute TM may be the extraintestinal manifestation of UC, which may be related to the abnormalities of cell-mediated and humoral immunity rather than the side effect of mesalazine.
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Affiliation(s)
- Yi Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, No. 37 Guoxue Road, Chengdu, 610041, China
| | - Yan Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, No. 37 Guoxue Road, Chengdu, 610041, China.
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12
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Zhang S, Chen F, Wu J, Liu C, Yang G, Piao R, Geng B, Xu K, Liu P. Regional Gray Matter Volume Changes in Brains of Patients With Ulcerative Colitis. Inflamm Bowel Dis 2022; 28:599-610. [PMID: 34734248 DOI: 10.1093/ibd/izab252] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) and Crohn's disease (CD) are 2 subtypes of inflammatory bowel disease (IBD). Several studies have reported brain abnormalities in IBD patients. This study aims to identify differences of gray matter volume (GMV) between patients with UC and healthy controls (HCs). METHODS Fifty-seven patients with UC and 40 HCs underwent structural magnetic resonance imaging. Voxel-based morphometry method was used to detect GMV differences. Receiver operating characteristic (ROC) curve was applied to investigate reliable biomarkers for identifying patients with UC from HCs. Regression analysis was used to examine relationships between the structure alternations and clinical symptoms. RESULTS Compared with HCs, patients with UC showed decreased GMV in the insula, thalamus, pregenual anterior cingulate cortex, hippocampus/parahippocampus, amygdala, and temporal pole; they showed increased GMV in the putamen, supplementary motor area, periaqueductal gray, hypothalamus, and precentral gyrus. Receiver operating characteristic analysis showed the highest classification power of thalamus. The inclusion of anxiety and depression as covariates eliminated the differences in the right insula, pregenual anterior cingulate cortex, supplementary motor area, and precentral gyrus. Most of the GMV changes were found in active patients with UC, with few changes in patients with UC in remission. We also found significantly negative correlation between UC duration and GMV in several regions. CONCLUSION The current neuroimaging findings were involved in visceral sensory pathways and were partially associated with the levels of anxiety and depression and clinical stage of patients with UC. This study might provide evidence for possible neuromechanisms of UC.
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Affiliation(s)
- Shuming Zhang
- Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, China
- Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, Xi'an, China
| | - Fenrong Chen
- Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jiayu Wu
- Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, China
- Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, Xi'an, China
| | - Chengxiang Liu
- Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, China
- Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, Xi'an, China
| | - Guang Yang
- Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, China
- Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, Xi'an, China
| | - Ruiqing Piao
- Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, China
- Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, Xi'an, China
| | - Bowen Geng
- Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, China
- Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, Xi'an, China
| | - Ke Xu
- Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, China
- Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, Xi'an, China
| | - Peng Liu
- Life Science Research Center, School of Life Science and Technology, Xidian University, Xi'an, China
- Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, Xi'an, China
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13
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El-Hakim Y, Bake S, Mani KK, Sohrabji F. Impact of intestinal disorders on central and peripheral nervous system diseases. Neurobiol Dis 2022; 165:105627. [PMID: 35032636 DOI: 10.1016/j.nbd.2022.105627] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 01/03/2022] [Accepted: 01/09/2022] [Indexed: 12/16/2022] Open
Abstract
Brain injuries and neurological diseases have a significant impact on the gut microbiome and the gut barrier. Reciprocally, gut disorders, such as Inflammatory Bowel Syndromes (IBS), can affect the development and pathology of neurodegenerative and neuropsychiatric diseases, although this aspect is less well studied and is the focus of this review. Inflammatory Bowel Syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder afflicting an estimated 9-23% of the world's population. A hallmark of this disease is leaky gut, a pathology in which the integrity of the gut blood barrier is compromised, causing gut contents such as immune cells and microbiota to enter the bloodstream leading to low-grade systemic inflammation. The increased levels of inflammation associated cytokines in circulation has the potential to affect all organs, including the brain. Although the brain is protected by the blood brain barrier, inflammation associated cytokines can damage the junctions in this barrier and allow brain infiltration of peripheral immune cells. Central inflammation in the brain is associated with various neurodegenerative disease such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and neuropsychiatric disorders, namely, depression, and anxiety. Neurodegenerative diseases are of particular concern due to the anticipated rise in the population of the elderly and consequently, the prevalence of these diseases. Additionally, depression and anxiety are the most common mental illnesses affecting roughly 18% of the American population. In this review, we will explore the mechanisms by which IBS can influence the risk and severity of neurological disease.
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Affiliation(s)
- Yumna El-Hakim
- Women's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health Science Center, Bryan, TX, USA
| | - Shameena Bake
- Women's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health Science Center, Bryan, TX, USA
| | - Kathiresh Kumar Mani
- Women's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health Science Center, Bryan, TX, USA
| | - Farida Sohrabji
- Women's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health Science Center, Bryan, TX, USA.
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14
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Hutto SK, Maher MD, Miloslavsky EM, Venna N. Nodular Pachymeningitis Associated With Relapsing Polychondritis and Crohn Disease Responsive to Adalimumab and Prednisone. NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION 2021; 8:8/5/e1022. [PMID: 34078656 PMCID: PMC8176555 DOI: 10.1212/nxi.0000000000001022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/05/2021] [Indexed: 11/30/2022]
Abstract
Objectives To review the previous literature on the associations of pachymeningitis with Crohn disease (CD) and relapsing polychondritis (RP) and to describe a new case occurring in association with both in addition to highlighting its positive response to steroid and adalimumab treatment. Methods We review the patient's clinical presentation, diagnostic workup (serum and CSF testing), and MRI findings in detail and chronicle the response of the pachymeningitis to intensive immunotherapy. We contrast this case against previous reports of pachymeningitis occurring in association with RP and inflammatory bowel disease that were found on PubMed. Results Only 2 cases of ulcerative colitis and 5 cases of RP were found in association with pachymeningitis; there were no cases in association with CD. Our patient presented with symptoms isolated to a steroid-responsive headache in the setting of normal neurologic and rheumatologic examinations. Her preceding history was notable for long-standing CD and increasingly active symptoms referable to RP. Focal nodular pachymeningitis was seen overlying the left hemisphere on brain MRI. An extensive serum and CSF workup and body fluorodeoxyglucose-PET scan failed to identify an alternative etiology beyond her underlying autoimmune inflammatory disorders. After adding prednisone and adalimumab to her preexisting treatment of methotrexate, she responded dramatically both clinically and radiographically. Conclusions Although exceptionally rare, pachymeningitis may occur as a neuroinflammatory complication of CD and RP.
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Affiliation(s)
- Spencer K Hutto
- From the Division of Neuroimmunology and Neuroinfectious Diseases (S.K.H., N.V.), Department of Neurology, Massachusetts General Hospital, Boston; Division of Neuroradiology (M.D.M), Department of Radiology, Massachusetts General Hospital, Boston; and Division of Rheumatology, Allergy and Immunology (E.M.M), Department of Medicine, Massachusetts General Hospital, Boston.
| | - Mary D Maher
- From the Division of Neuroimmunology and Neuroinfectious Diseases (S.K.H., N.V.), Department of Neurology, Massachusetts General Hospital, Boston; Division of Neuroradiology (M.D.M), Department of Radiology, Massachusetts General Hospital, Boston; and Division of Rheumatology, Allergy and Immunology (E.M.M), Department of Medicine, Massachusetts General Hospital, Boston
| | - Eli M Miloslavsky
- From the Division of Neuroimmunology and Neuroinfectious Diseases (S.K.H., N.V.), Department of Neurology, Massachusetts General Hospital, Boston; Division of Neuroradiology (M.D.M), Department of Radiology, Massachusetts General Hospital, Boston; and Division of Rheumatology, Allergy and Immunology (E.M.M), Department of Medicine, Massachusetts General Hospital, Boston
| | - Nagagopal Venna
- From the Division of Neuroimmunology and Neuroinfectious Diseases (S.K.H., N.V.), Department of Neurology, Massachusetts General Hospital, Boston; Division of Neuroradiology (M.D.M), Department of Radiology, Massachusetts General Hospital, Boston; and Division of Rheumatology, Allergy and Immunology (E.M.M), Department of Medicine, Massachusetts General Hospital, Boston
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15
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Steriade C, Titulaer MJ, Vezzani A, Sander JW, Thijs RD. The association between systemic autoimmune disorders and epilepsy and its clinical implications. Brain 2021; 144:372-390. [PMID: 33221878 DOI: 10.1093/brain/awaa362] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 08/03/2020] [Accepted: 08/13/2020] [Indexed: 12/12/2022] Open
Abstract
Systemic autoimmune disorders occur more frequently in patients with epilepsy than in the general population, suggesting shared disease mechanisms. The risk of epilepsy is elevated across the spectrum of systemic autoimmune disorders but is highest in systemic lupus erythematosus and type 1 diabetes mellitus. Vascular and metabolic factors are the most important mediators between systemic autoimmune disorders and epilepsy. Systemic immune dysfunction can also affect neuronal excitability, not only through innate immune activation and blood-brain barrier dysfunction in most epilepsies but also adaptive immunity in autoimmune encephalitis. The presence of systemic autoimmune disorders in subjects with acute seizures warrants evaluation for infectious, vascular, toxic and metabolic causes of acute symptomatic seizures, but clinical signs of autoimmune encephalitis should not be missed. Immunosuppressive medications may have antiseizure properties and trigger certain drug interactions with antiseizure treatments. A better understanding of mechanisms underlying the co-existence of epilepsy and systemic autoimmune disorders is needed to guide new antiseizure and anti-epileptogenic treatments. This review aims to summarize the epidemiological evidence for systemic autoimmune disorders as comorbidities of epilepsy, explore potential immune and non-immune mechanisms, and provide practical implications on diagnostic and therapeutic approach to epilepsy in those with comorbid systemic autoimmune disorders.
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Affiliation(s)
- Claude Steriade
- Department of Neurology, New York University School of Medicine, New York, NY, USA
| | - Maarten J Titulaer
- Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Annamaria Vezzani
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Josemir W Sander
- NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.,Chalfont Centre for Epilepsy, Chalfont St Peter SL9 0RJ, Bucks, UK.,Stichting Epilepsie Instellingen Nederland - (SEIN), Heemstede, The Netherlands
| | - Roland D Thijs
- NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.,Stichting Epilepsie Instellingen Nederland - (SEIN), Heemstede, The Netherlands.,Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
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16
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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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17
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Abstract
PURPOSE OF REVIEW This article describes the neurologic sequelae of various nutritional micronutrient deficiencies, celiac disease, inflammatory bowel disease, and liver disease. Where relevant, appropriate treatments for these conditions are also discussed. The developing field of the microbiome and nervous system interaction is also outlined. RECENT FINDINGS Pathology in the gastrointestinal system can affect the nervous system when it causes micronutrient deficiency, when immune responses created by the gastrointestinal system affect the nervous system, when toxins caused by gastrointestinal organ failure harm the nervous system, and when treatments aimed at a gastrointestinal medical condition cause damage to the nervous system as a side effect. SUMMARY This article addresses familiar concepts and new developments in the treatment and understanding of diseases that affect the gut and nervous system simultaneously.
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18
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Malik A, Berry R, Fung BM, Tabibian JH. Association between chronic inflammatory demyelinating polyneuropathy and gastrointestinal malignancies. Clin J Gastroenterol 2021; 14:1-13. [PMID: 33146871 DOI: 10.1007/s12328-020-01281-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 10/20/2020] [Indexed: 11/29/2022]
Abstract
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon and under-recognized immune-mediated disorder of the peripheral nervous system. It is associated with both infectious and non-infectious etiologies and presents in several variant forms. In rare instances, CIDP has been reported in association with gastrointestinal (esophageal, hepatic, colorectal, and pancreatic) malignancies. The diagnosis of malignancy is typically preceded by weeks to months by that of CIDP, though the inverse may also be seen. As with other etiologies of CIDP, cases associated with gastrointestinal malignancies are often treated with corticosteroids, intravenous immunoglobulins, and/or plasma exchange, with improvement or resolution of neurological symptoms in the majority of cases. In this review, we provide a practical overview of CIDP, with an emphasis on recognizing the clinical association between CIDP and gastrointestinal malignancies.
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Affiliation(s)
- Adnan Malik
- Division of Hepatology, Loyola University Medical Center, Maywood, IL, USA
| | - Rani Berry
- Department of Internal Medicine, UCLA Ronald Reagan Medical Center, Los Angeles, CA, USA
| | - Brian M Fung
- Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - James H Tabibian
- Division of Gastroenterology, Olive View-UCLA Medical Center, 14445 Olive View Dr, Sylmar, CA, 2B-182, USA.
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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19
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Hanscom M, Loane DJ, Aubretch T, Leser J, Molesworth K, Hedgekar N, Ritzel RM, Abulwerdi G, Shea-Donohue T, Faden AI. Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits. J Neuroinflammation 2021; 18:24. [PMID: 33461596 PMCID: PMC7814749 DOI: 10.1186/s12974-020-02067-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/21/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Disruptions of brain-gut axis have been implicated in the progression of a variety of gastrointestinal (GI) disorders and central nervous system (CNS) diseases and injuries, including traumatic brain injury (TBI). TBI is a chronic disease process characterized by persistent secondary injury processes which can be exacerbated by subsequent challenges. Enteric pathogen infection during chronic TBI worsened cortical lesion volume; however, the pathophysiological mechanisms underlying the damaging effects of enteric challenge during chronic TBI remain unknown. This preclinical study examined the effect of intestinal inflammation during chronic TBI on associated neurobehavioral and neuropathological outcomes, systemic inflammation, and dysautonomia. METHODS Dextran sodium sulfate (DSS) was administered to adult male C57BL/6NCrl mice 28 days following craniotomy (Sham) or TBI for 7 days to induce intestinal inflammation, followed by a return to normal drinking water for an additional 7 to 28 days for recovery; uninjured animals (Naïve) served as an additional control group. Behavioral testing was carried out prior to, during, and following DSS administration to assess changes in motor and cognitive function, social behavior, and mood. Electrocardiography was performed to examine autonomic balance. Brains were collected for histological and molecular analyses of injury lesion, neurodegeneration, and neuroinflammation. Blood, colons, spleens, mesenteric lymph nodes (mLNs), and thymus were collected for morphometric analyses and/or immune characterization by flow cytometry. RESULTS Intestinal inflammation 28 days after craniotomy or TBI persistently induced, or exacerbated, respectively, deficits in fine motor coordination, cognition, social behavior, and anxiety-like behavior. Behavioral changes were associated with an induction, or exacerbation, of hippocampal neuronal cell loss and microglial activation in Sham and TBI mice administered DSS, respectively. Acute DSS administration resulted in a sustained systemic immune response with increases in myeloid cells in blood and spleen, as well as myeloid cells and lymphocytes in mesenteric lymph nodes. Dysautonomia was also induced in Sham and TBI mice administered DSS, with increased sympathetic tone beginning during DSS administration and persisting through the first recovery week. CONCLUSION Intestinal inflammation during chronic experimental TBI causes a sustained systemic immune response and altered autonomic balance that are associated with microglial activation, increased neurodegeneration, and persistent neurological deficits.
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Affiliation(s)
- Marie Hanscom
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA.
| | - David J Loane
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland
| | - Taryn Aubretch
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA
| | - Jenna Leser
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA
| | - Kara Molesworth
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA
| | - Nivedita Hedgekar
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA
| | - Rodney M Ritzel
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA
| | - Gelareh Abulwerdi
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA
| | - Terez Shea-Donohue
- Division of Translational Radiation Sciences (DTRS), Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Alan I Faden
- Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF #6-016, Baltimore, MD, 21201, USA
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20
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Yasuda T, Takagi T, Hasegawa D, Hirose R, Inoue K, Dohi O, Yoshida N, Kamada K, Uchiyama K, Ishikawa T, Konishi H, Naito Y, Itoh Y. Multiple Cerebral Infarction Associated with Cerebral Vasculitis in a Patient with Ulcerative Colitis. Intern Med 2021; 60:59-66. [PMID: 32830176 PMCID: PMC7835462 DOI: 10.2169/internalmedicine.4951-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 07/01/2020] [Indexed: 11/18/2022] Open
Abstract
A 40-year-old man was admitted to the hospital due to both a worsening of symptoms associated with ulcerative colitis (UC), which had been diagnosed 3 years previously, and limb paralysis. Colonoscopy revealed severe pancolitis-type UC. He was diagnosed with cerebral vasculitis with multiple white matter infarctions associated with the disease activity of UC by contrast-enhanced head magnetic resonance imaging. Mesalazine at 4,000 mg/day and prednisolone at 60 mg/day were started, and the prednisolone dosage was thereafter gradually reduced and switched to golimumab. He achieved a long-term remission from UC, and thereafter his neurological abnormalities improved significantly. He had no recurrence of cerebral infarction.
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Affiliation(s)
- Takeshi Yasuda
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Tomohisa Takagi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Daisuke Hasegawa
- Department of Gastroenterology and Hepatology, Ayabe City Hospital, Japan
| | - Ryohei Hirose
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Ken Inoue
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Osamu Dohi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Naohisa Yoshida
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Kazuhiro Kamada
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Kazuhiko Uchiyama
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Takeshi Ishikawa
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Hideyuki Konishi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Yuji Naito
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
| | - Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
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21
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Crohn-related Chronic Relapsing Inflammatory Optic Neuropathy. Can J Neurol Sci 2020; 48:740-741. [PMID: 33308333 DOI: 10.1017/cjn.2020.270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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22
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Hoekstra E, Keunen R, van der Voorn M. Inability to walk: a rare presentation of Crohn's disease. BMJ Open Gastroenterol 2020; 7:bmjgast-2020-000526. [PMID: 33214233 PMCID: PMC7678226 DOI: 10.1136/bmjgast-2020-000526] [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: 08/29/2020] [Revised: 10/15/2020] [Accepted: 10/20/2020] [Indexed: 11/14/2022] Open
Abstract
A wide variety of extraintestinal manifestations of inflammatory bowel disease (IBD) have been described, with joint or dermatological complaints as most prevalent. However, also neurological manifestations can occur, which are rarely recognised and therefore under-reported. We present an very unusual case of a young man who presented with the inability to walk, as a first presentations of IBD.
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Affiliation(s)
- Elmer Hoekstra
- Department of Gastroenterology and Hepatology, Leiden Universitair Medisch Centrum, Leiden, Netherlands
| | - Rudolf Keunen
- Department of Neurology, Haga Ziekenhuis, Den Haag, Netherlands
| | - Michael van der Voorn
- Department of Gastroenterology and Hepatology, Haga Ziekenhuis, Den Haag, Netherlands
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Coe CL, Horst SN, Izzy MJ. Neurologic Toxicities Associated with Tumor Necrosis Factor Inhibitors and Calcineurin Inhibitors. Neurol Clin 2020; 38:937-951. [PMID: 33040870 DOI: 10.1016/j.ncl.2020.07.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The calcineurin inhibitors cyclosporine and tacrolimus are used for their immunosuppressive effects. Neurotoxic side effects include tremor, paresthesia, and headache. Rarer neurotoxicities include seizure, posterior reversible encephalopathy syndrome, and encephalopathy. Tacrolimus tends to be more neurotoxic than cyclosporine. Management of toxicities associated with calcineurin inhibitors includes dose reduction, switching between calcineurin inhibitors, or switching to a calcineurin-free regimen. Tumor necrosis factor (TNF) inhibitors are used in autoimmune diseases. Management of demyelinating conditions among patients treated with anti-TNF should follow standard of care and withdrawal of the anti-TNF. This drug class should be avoided in patients with a history of demyelinating conditions.
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Affiliation(s)
- Christopher L Coe
- Department of Medicine, Section of Hospital Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA. https://twitter.com/ccoemd
| | - Sarah N Horst
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 1211 21st Avenue South, Medical Arts Building, Suite 220, Nashville, TN 37232, USA. https://twitter.com/HorstIBDDoc
| | - Manhal J Izzy
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Transplant Hepatology, 1660 The Vanderbilt Clinic, Nashville, TN 37232, USA.
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Importance of Not MSing Cerebral White Matter Disease in Patients with Inflammatory Bowel Disease. Dig Dis Sci 2020; 65:2527-2532. [PMID: 32651742 DOI: 10.1007/s10620-020-06449-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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25
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Sanchez JMS, McNally JS, Cortez MM, Hemp J, Pace LA, Clardy SL. Neuroimmunogastroenterology: At the Interface of Neuroimmunology and Gastroenterology. Front Neurol 2020; 11:787. [PMID: 32849234 PMCID: PMC7412790 DOI: 10.3389/fneur.2020.00787] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 06/25/2020] [Indexed: 12/11/2022] Open
Abstract
The central nervous system (CNS) is an important regulator of the gastrointestinal tract, and CNS dysfunction can result in significant and disabling gastrointestinal symptom manifestation. For patients with neuroimmunologic and neuroinflammatory conditions, the recognition of gastrointestinal symptoms is under-appreciated, yet the gastrointestinal manifestations have a dramatic impact on quality of life. The current treatment strategies, often employed independently by the neurologist and gastroenterologist, raise the question of whether such patients are being treated optimally when siloed in one specialty. Neuroimmunogastroenterology lies at the borderlands of medical specialties, and there are few resources to guide neurologists in this area. Here, we provide an overview highlighting the potential mechanisms of crosstalk between immune-mediated neurological disorders and gastrointestinal dysfunction.
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Affiliation(s)
- John Michael S. Sanchez
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT, United States
| | - J. Scott McNally
- Department of Radiology, Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, UT, United States
| | - Melissa M. Cortez
- Department of Neurology, Imaging and Neurosciences Center, University of Utah, Salt Lake City, UT, United States
| | - James Hemp
- Division of Gastroenterology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States
| | - Laura A. Pace
- Division of Gastroenterology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States
| | - Stacey L. Clardy
- Department of Neurology, Imaging and Neurosciences Center, University of Utah, Salt Lake City, UT, United States
- George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT, United States
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26
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Neuropathy and primary headaches affect different subgroups of inflammatory bowel disease patients. Neurol Sci 2020; 42:935-942. [PMID: 32671582 DOI: 10.1007/s10072-020-04596-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 07/11/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Peripheral neuropathies (PN) and primary headaches (PH) are common comorbidities in inflammatory bowel disease (IBD) patients. We aimed to evaluate whether PN and PH affect the same subgroups of IBD patients. METHODS Since 2004, we established a cohort study to evaluate neurological diseases in IBD patients. Over 2 years, all consecutive (N = 155) IBD patients (either Crohn's disease (CD) or ulcerative colitis (UC) were evaluated for the presence of PN and PH. PH were also evaluated in dyspeptic patients (N = 84) and IBD relatives (controls, N = 101). After neurological evaluation, symptomatic patients underwent skin wrinkling test to evaluate small fiber function and/or electromyography. RESULTS Headaches and migraine were more prevalent in IBD than control patients: 52.3 and 34.2% vs. 40.6 and 20.8% (P < 0.05). Migraine was 2.6 times more common in CD patients than controls (CI = 1.34-5.129) and 8.6 times (13.3 times in the CD group) more common in men with IBD (P < 0.05). Headache and migraine were also more common in dyspeptic patients (P < 0.05). Chi-square, univariate, and multivariate regression analysis did not disclose any association between PN, headache, or PH (P > 0.05). Multivariate regression analysis disclosed that headaches were more prevalent in women, co-existing psychiatric disease, IBD, CD, and UC. After age, gender distribution, and prevalence of hypertension and psychiatric diseases were matched among the groups, there were still differences in the prevalence of headaches and migraine among IBD, CD, and UC versus control patients. CONCLUSION In summary, PH and PN are common in IBD and do not affect the same subgroups of patients.
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Abstract
Abstract
Intestinal sarcoidosis can mimic Crohn disease (CD), and it is important to evaluate for alternative diagnoses in patients who present with atypical symptoms or do not respond to conventional therapy. Furthermore, CD, with or without biologic therapy, has been associated with neurological symptoms including neuropathies, myelopathies, thromboembolic, and demyelinating diseases leading to diagnostic uncertainty. We present a case of sarcoidosis of the luminal gastrointestinal tract and central nervous system, which mimicked the presentation of CD. This case highlights the need to expand the differential diagnosis in patients who present with atypical symptoms and do not respond to biologic therapy.
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Affiliation(s)
- Jonah N Rubin
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD
| | - Lauren A George
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD
| | - Raymond K Cross
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD
| | - Uni Wong
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD
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28
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Nemati R, Mehdizadeh S, Salimipour H, Yaghoubi E, Alipour Z, Tabib SM, Assadi M. Neurological manifestations related to Crohn's disease: a boon for the workforce. Gastroenterol Rep (Oxf) 2019; 7:291-297. [PMID: 31413837 PMCID: PMC6688734 DOI: 10.1093/gastro/gox034] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 07/28/2017] [Accepted: 08/22/2017] [Indexed: 12/26/2022] Open
Abstract
The neurological manifestations of Crohn's disease and its prevalence are not well known. Here, we report five patients of confirmed Crohn's disease with different neurological presentations. The neurological presentations include anterior ischemic optic neuropathy, myelopathy, posterior reversible encephalopathy syndrome, chronic inflammatory demyelinating polyneuropathy, and chronic axonal sensory and motor polyneuropathy. These manifestations should be kept in mind in the assessment of Crohn's disease.
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Affiliation(s)
- Reza Nemati
- Department of Neurology, Bushehr University of Medical Sciences, Bushehr, Iran.,The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Somayeh Mehdizadeh
- Department of Pathology, Rasul-e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Hooman Salimipour
- Department of Neurology, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Ehsan Yaghoubi
- Department of Neurology, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Zeinab Alipour
- Department of Gastroenterology and Hepatology, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Seyed Masoud Tabib
- Department of Gastroenterology and Hepatology, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Majid Assadi
- The Persian Gulf Nuclear Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran
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29
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Vojdani A. Is there a possible correlation between antibodies against lipopolysaccharide, intestinal and blood-brain barrier proteins in IBD subjects? Clin Exp Rheumatol 2019; 18:639-641. [DOI: 10.1016/j.autrev.2019.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 01/31/2019] [Indexed: 02/07/2023]
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Annese V. A Review of Extraintestinal Manifestations and Complications of Inflammatory Bowel Disease. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2019; 7:66-73. [PMID: 31080385 PMCID: PMC6503692 DOI: 10.4103/sjmms.sjmms_81_18] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Extraintestinal manifestations (EIMs) are common in inflammatory bowel disease (IBD), in both Crohn's disease and ulcerative colitis. Almost any organ system can be affected, including the musculoskeletal, dermatologic, renal, hepatopancreatobiliary, pulmonary and ocular systems. However, the musculoskeletal and dermatologic systems are the most commonly involved sites of manifestations. While some manifestations such as peripheral arthritis and erythema nodosum have an association with IBD activity, others such as axial arthropathy, pyoderma gangrenosum and primary sclerosing cholangitis have an independent disease course. This review provides a summary of the most common EIMs in IBD and their prevalence and management.
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Affiliation(s)
- Vito Annese
- Department of Gastroenterology, Valiant Clinic, Dubai, United Arab Emirates
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31
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Kelleci UA, Calhan T, Sahin A, Aydin-Ozemir Z, Kahraman R, Ozdil K, Sokmen HM, Yalcin AD. Electroencephalography Findings in Crohn's Disease. Clin EEG Neurosci 2019; 50:129-133. [PMID: 29707968 DOI: 10.1177/1550059418767589] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Crohn's Disease (CD) is a chronic systemic inflammatory disease associated with various extraintestinal manifestations, including seizure as a neurological finding. In this study, the prevalence of seizure and electroencephalographic abnormalities in patients with CD was investigated. MATERIALS AND METHODS This study involved 41 patients with CD (female/male: 25/16) and 39 subjects in the control group (female/male: 25/14). Patients in the CD group were diagnosed and monitored according to the European Crohn's and Colitis Organization diagnostic criteria. The control group was composed of healthy subjects with similar age and sex as the CD group. Seizures were classified according to the criteria of the International League Against Epilepsy. Electroencephalography (EEG) was performed for all patients with CD and for healthy subjects. Seizure prevalence and EEG findings were also compared. RESULTS One patient in the CD group had history of seizures. EEG abnormality was significantly higher in the CD group (16/41, 39%) ( P = .001). The most common EEG abnormality was intermittent generalized slow wave abnormality in theta frequency. DISCUSSION Our study indicated that CD was associated with EEG abnormalities rather than seizure. The results also indicated that EEG was a potential indicator for detecting subclinical neurological abnormalities in CD.
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Affiliation(s)
| | - Turan Calhan
- 1 University of Health Sciences, Umraniye, Istanbul, Turkey
| | | | | | - Resul Kahraman
- 1 University of Health Sciences, Umraniye, Istanbul, Turkey
| | - Kamil Ozdil
- 1 University of Health Sciences, Umraniye, Istanbul, Turkey
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Parks PT, Easton AS. Cerebral Vasculitis in Ulcerative Colitis Is Predominantly Venular: Case Report and Review of the Literature. Case Rep Rheumatol 2019; 2019:9563874. [PMID: 30937208 PMCID: PMC6413389 DOI: 10.1155/2019/9563874] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 01/27/2019] [Accepted: 02/12/2019] [Indexed: 11/19/2022] Open
Abstract
Extraintestinal complications of ulcerative colitis include isolated case reports of cerebral vasculitis. In this case report, we describe autopsy findings in a 50-year-old female who died as a result of massive multifocal cerebral hemorrhage. Microscopic examination of the left colon showed findings typical for ulcerative colitis. Examination of the brain showed an extensive vasculitis. More affected vessels were noted in grey matter than in white matter. Many showed fibrinoid necrosis, invasion by neutrophils and thrombosis. There was extensive perivascular hemorrhage with associated infarction. Vessel analysis shows most of the vessels to have been venous rather than arterial. There were no perivascular sleeves of demyelination to suggest a primary demyelinating disorder, such as acute hemorrhagic leucoencephalitis. Our analysis shows that veins are the likely target of cerebral vasculitis in ulcerative colitis. This has clinical implications because venous occlusion generally causes massive intracerebral hemorrhage with a high mortality.
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Affiliation(s)
- Paul T. Parks
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Tominaga K, Tsuchiya A, Sato H, Kimura A, Oda C, Hosaka K, Kawata Y, Kimura N, Hayashi K, Yokoyama J, Terai S. Co-existent ulcerative colitis and Guillain-Barré syndrome: a case report and literature review. Clin J Gastroenterol 2019; 12:243-246. [PMID: 30778832 DOI: 10.1007/s12328-019-00939-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 01/15/2019] [Indexed: 12/25/2022]
Abstract
Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease involving the intestine, and Guillain-Barré Syndrome (GBS) is rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. UC and GBS can be caused by immune system abnormalities and can co-exist. To date, there are 7 reported cases of GBS in patients with UC. However, only one patient developed UC after GBS treatment. We report a rare case of UC that appeared after intravenous immunoglobulin therapy for GBS. This case report and literature review will allow accurate and prompt diagnosis of co-existent GBS and UC.
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Affiliation(s)
- Kentaro Tominaga
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan.
| | - Hiroki Sato
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Atsushi Kimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Chiyumi Oda
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Kazunori Hosaka
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Yuzo Kawata
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Naruhiro Kimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Kazunao Hayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, Niigata, 9518510, Japan
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Whittaker K, Guggenberger K, Venhoff N, Doostkam S, Schaefer HE, Fritsch B. Cerebral granulomatosis as a manifestation of Crohn's disease. BMC Neurol 2018; 18:161. [PMID: 30285676 PMCID: PMC6169107 DOI: 10.1186/s12883-018-1163-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 09/24/2018] [Indexed: 10/07/2023] Open
Abstract
BACKGROUND Crohn's disease (CD) is associated with a variety of extra-intestinal manifestations. Most commonly these involve the eye, skin, joints, coagulation system and liver. Cerebral manifestations of CD have been reported to a far lesser extent. The extensive detrimental impact of neurological symptoms on a patient's quality of life makes an early diagnosis and treatment particularly important. In previous case-reports, diagnosis of cerebral manifestations in CD often relied upon magnetic resonance imaging (MRI) and computed tomography (CT) alone. To our knowledge, only one case-report has documented a histologically confirmed case of cerebral lesions associated with CD so far. CASE PRESENTATION A 39-year-old right-handed woman with a history of CD was referred to our hospital with etiologically unexplained Gadolinium (Gd)-enhancing cortical lesions, triggering epileptic seizures. A CT-scan of the thorax and bronchoalveolar lavage found no signs of sarcoidosis. Lumbar punctures and laboratory testing found no underlying infection or coincidental autoimmune disorders and MRI-scans showed progression of lesion load. Consequently, the patient underwent stereotactic biopsy of a cortical lesion. Histological examination revealed a mixed lympho-histiocytic and tuberculoid granulomatous inflammation surrounding small vessels and no signs for infection. After exclusion of other granulomatous diseases and the typical histological findings we diagnosed a cerebral granulomatosis as a manifestation of CD. The patient was initially started on azathioprine, which had to be switched to corticosteroids and methotrexate because of an azathioprine related pancreatitis. The patient has not suffered any further epileptic seizures to date. CONCLUSION Cerebral manifestation of CD is a possibly underreported entity that may respond well to immunosuppressive treatment. In contrast to earlier reports of cerebral manifestations in CD, our patient showed no coincident gastrointestinal symptoms indicating an activity of CD during the progression of cortical lesion load, suggesting that similar to other extra-intestinal manifestations in CD, the activity of gastrointestinal symptoms does not necessarily reflect the activity of CD associated cerebral vasculitis. Therefore, diagnosis and therapy of cerebral manifestation may be delayed when focusing on gastrointestinal symptoms alone.
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Affiliation(s)
- Konrad Whittaker
- Department of Neurology and Neuroscience, Medical Center, University of Freiburg, Breisacher Straße 64, D-79106, Freiburg, Germany.
| | - Konstanze Guggenberger
- Department of Neuroradiology, University of Freiburg, Breisacher Straße 64, D-79106, Freiburg, Germany
| | - Nils Venhoff
- Department of Rheumatology and Clinical Immunology, University of Freiburg, Breisacher Straße 64, D-79106, Freiburg, Germany
| | - Soroush Doostkam
- Department of Neuropathology, University of Freiburg, Breisacher Straße 64, D-79106, Freiburg, Germany
| | - Hans-Eckart Schaefer
- Department of Clinical Pathology, University of Freiburg, Breisacher Straße 64, D-79106, Freiburg, Germany
| | - Brita Fritsch
- Department of Neurology and Neuroscience, Medical Center, University of Freiburg, Breisacher Straße 64, D-79106, Freiburg, Germany
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Abstract
PURPOSE OF REVIEW Just as gastrointestinal dysfunction may develop in the setting of neurologic disease, neurologic dysfunction may become evident in the setting of gastrointestinal disease. This article describes the range of neurologic features that have been described in three primary gastrointestinal diseases: celiac disease and gluten-related disorders, inflammatory bowel disease, and Whipple disease. Particular emphasis is placed on the controversial and evolving clinical picture of neurologic dysfunction in disorders of gluten sensitivity. RECENT FINDINGS Gluten-related disorders, including both the traditional autoimmune-based celiac disease and the more recently recognized nonautoimmune, nonallergic gluten sensitivity, have been the source of much attention in both medical and lay publications. The possible association between Crohn disease and neurologic disorders also is receiving attention. The recognition that, although Whipple disease is an exceedingly rare disorder, a surprising percentage of the population may be asymptomatic stool carriers of the causative organism makes it important to always be cognizant of the disorder. SUMMARY The range of neurologic dysfunction in gastrointestinal diseases is broad and spans the spectrum from peripheral to central processes. Peripheral neuropathy, myopathy, myelopathy, cerebrovascular events, epilepsy, encephalopathy, and cerebellar dysfunction have all been described. Neurologists should be aware of the possibility that an underlying gastrointestinal disease process may be present in and responsible for the neurologic dysfunction that has prompted referral of an individual for evaluation.
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Endres K, Schäfer KH. Influence of Commensal Microbiota on the Enteric Nervous System and Its Role in Neurodegenerative Diseases. J Innate Immun 2018; 10:172-180. [PMID: 29742516 DOI: 10.1159/000488629] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 03/14/2018] [Indexed: 12/12/2022] Open
Abstract
When thinking about neurodegenerative diseases, the first symptoms that come to mind are loss of memory and learning capabilities, which all resemble hallmarks of manifestation of such diseases in the central nervous system (CNS). However, the gut comprises the largest nervous system outside the CNS that is autonomously active and in close interplay with its microbiota. Therefore, the enteric nervous system (ENS) might serve as an indicator of degenerative pathomechanisms that also affect the CNS. On the other hand, it might offer an entry point for devastating influences from the microbial community or - conversely - for therapeutic approaches via gut commensals. Within the last years, the ENS and gut microbiota therefore have sparked the interest of researchers of CNS diseases and we here report on recent findings and open questions, especially with regard to Alzheimer and Parkinson diseases.
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Affiliation(s)
- Kristina Endres
- Department of Psychiatry and Psychotherapy, Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Karl-Herbert Schäfer
- University of Applied Sciences Kaiserslautern, Campus Zweibrücken, Zweibrücken, Germany
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37
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Park MR, Min MK, Ryu JH, Lee DS, Lee KH. Multiple cerebral infarct with cerebral vasculitis in a young patient with ulcerative colitis. Am J Emerg Med 2018; 36:733.e3-733.e5. [PMID: 29325982 DOI: 10.1016/j.ajem.2018.01.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 12/28/2017] [Accepted: 01/03/2018] [Indexed: 01/06/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic and debilitating disorder, characterized by inflammation of the colonic mucosa. UC can be considered a systemic disorder but UC-related manifestations in the central nervous system (CNS) are quite rare. A 29-year-old man was admitted to the emergency department with repeated generalized tonic-clonic (GTC) type seizures. Based on brain CT, brain metastasis or hemorrhagic infarct was suspected. Diffusion-weighted image of brain MRI showed high signal in the left thalamus and heterogenous enhancement in the right parietal and left frontal lobes. This image indicated a cerebral infarct, but could not completely rule out cerebral metastasis and vasculitis, or any other pathology. However, the brain biopsy revealed multiple thromboemboli with acute inflammation and necrosis. Thus, the patient was diagnosed with multiple cerebral infarcts with cerebral vasculitis, occurring as a complication of UC. In conclusion, CNS manifestations of UC are rare. However, clinicians should consider uncommon diagnoses like vasculitis and thromboembolism in patients with UC presenting with seizures.
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Affiliation(s)
- Maeng Real Park
- Department of Emergency Medicine, Pusan National University Yangsan Hospital, South Korea
| | - Mun Ki Min
- Department of Emergency Medicine, Pusan National University Yangsan Hospital, South Korea.
| | - Ji Ho Ryu
- Department of Emergency Medicine, Pusan National University Yangsan Hospital, South Korea
| | - Dae Sub Lee
- Department of Emergency Medicine, Pusan National University Yangsan Hospital, South Korea
| | - Kang Ho Lee
- Department of Emergency Medicine, Pusan National University Yangsan Hospital, South Korea
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Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. Application of carbon nanotubes as the carriers of the cannabinoid, 2-arachidonoylglycerol: Towards a novel treatment strategy in colitis. Life Sci 2017; 179:66-72. [DOI: 10.1016/j.lfs.2016.11.015] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 11/09/2016] [Accepted: 11/20/2016] [Indexed: 12/25/2022]
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Fiorino G, Bonovas S, Cicerone C, Allocca M, Furfaro F, Correale C, Danese S. The safety of biological pharmacotherapy for the treatment of ulcerative colitis. Expert Opin Drug Saf 2017; 16:437-443. [PMID: 28279079 DOI: 10.1080/14740338.2017.1298743] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Biological agents are effective in ulcerative colitis (UC). Currently, 3 anti-TNF agents (infliximab, adalimumab, and golimumab) and 1 anti-integrin agent (vedolizumab) are approved for the treatment of UC. The mechanism of action of biologic agents can also give rise to several side effects, some even serious. It remains uncertain to what extent biologic treatments may be associated with an increased rate of infections, malignancies and other adverse events Areas covered: Our aim is to review the relevant data available in the literature and briefly summarize the safety profile of biological therapy in UC. We performed a literature search using the OVID, MEDLINE, PUBMED and EMBASE databases. Also other relevant sources of safety data were also used. Expert opinion: All biological agents currently used in UC are relatively safe. Accurate prevention measures and screening prior to start such therapies, and regular surveillance programs are strongly recommend to minimize any risk of infections, malignancy and other adverse events related to the use of monoclonal antibodies in UC patients.
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Affiliation(s)
- Gionata Fiorino
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Stefanos Bonovas
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Clelia Cicerone
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Mariangela Allocca
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Federica Furfaro
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Carmen Correale
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Silvio Danese
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy.,b Department of Biomedical Sciences , Humanitas University , Milan , Italy
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Abstract
Differentiating Guillain-Barré syndrome (GBS) from inherited neuropathies and other acquired peripheral neuropathies requires understanding the atypical presentations of GBS and its variant forms, as well as historical and physical features suggestive of inherited neuropathies. GBS is typically characterized by the acute onset of ascending flaccid paralysis, areflexia, and dysesthesia secondary to peripheral nerve fiber demyelination. The disorder usually arises following a benign gastrointestinal or respiratory illness, is monophasic, reaches a nadir with several weeks, and responds to immunomodulatory therapy. Inherited neuropathies with onset before adulthood, whose presentation may mimic Guillain-Barré syndrome, are reviewed.
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Affiliation(s)
- Brett J Bordini
- Department of Pediatrics, Section of Hospital Medicine, Nelson Service for Undiagnosed and Rare Diseases, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA.
| | - Priya Monrad
- Department of Child and Adolescent Neurology, Medical College of Wisconsin, Milwaukee, WI, USA
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41
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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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42
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Kirito Y, Yamamoto D, Uchiyama T. Proteinase 3-antineutrophil cytoplasmic antibody-positive ulcerative colitis presenting with abducens neuropathy. BMJ Case Rep 2017; 2017:bcr-2016-218353. [PMID: 28069788 PMCID: PMC5256449 DOI: 10.1136/bcr-2016-218353] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
A 72-year-old man with ulcerative colitis (UC) presented with complete left abducens nerve palsy. Although MRI showed no significant changes, cerebrospinal fluid analysis revealed pleocytosis and elevated protein and interleukin (IL)-6 levels. His serum proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) level was also elevated to 31.1 U/mL, but granulomatosis with polyangiitis was not observed. On the basis of the diagnosis of autoimmune cranial neuropathy, he was treated with steroid therapy. While tapering steroid therapy, his serum PR3-ANCA levels; cerebrospinal fluid findings, including IL-6 levels; and symptoms improved. Serum PR3-ANCA could be a useful parameter of neurological disorders associated with ANCA-positive UC.
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Affiliation(s)
- Yuki Kirito
- Department of Neurology, Seirei Hamamatu General Hospital, Hamamatsu, Shizuoka, Japan
| | - Daisuke Yamamoto
- Department of Neurology, Seirei Hamamatu General Hospital, Hamamatsu, Shizuoka, Japan
| | - Tsuyoshi Uchiyama
- Department of Neurology, Seirei Hamamatu General Hospital, Hamamatsu, Shizuoka, Japan
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43
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Chehel Cheraghi S, Ebrahimi Daryani N, Ghabaee M. A Survey on Migraine Prevalence in Patients with Inflammatory Bowel Disease - A Single Centre Experience. Middle East J Dig Dis 2016; 8:282-288. [PMID: 27957291 PMCID: PMC5145295 DOI: 10.15171/mejdd.2016.37] [Citation(s) in RCA: 12] [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] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND It is hypothesized that migraine may be related to inflammatory bowel disease (IBD), therefore in this cross-sectional study we evaluated the prevalence of migraine in patients with IBD. METHODS In this cross-sectional study 80 patients with IBD and 80 patients without IBD referring to a private gastroenterology clinic from May to January 2014 were evaluated regarding the prevalence of migraine, severity of migraine based on Headache Impact Test (HIT-6), and habits related to headache. RESULTS
160 participants with the mean age of 35 years were evaluated. The prevalence of migraine in the case group was significantly higher than the control (21.3% vs. 8.8%, p=0.027). Moreover, duration of each attack (hours) in IBD group was significantly higher than the control group (p<0.001) while the duration of migraine involvement (months) and number of attacks was higher in the control group (p=0.019 and 0.048, respectively). Headache other than migraine in the control group was significantly higher than the IBD group(p<0.001). Disability in the case group was more than the control group but the difference was not significant. The correlation between the severity of disability related to migraine (based on HIT-6) and severity of IBD (based on May oscore & Crohn’s disease activity index (CDAI)) was not significant (r=0.16, p=0.58). Moreover the correlation between the duration of IBD and migraineprevalence was not significant (r=-0.14, p=0.19).
CONCLUSION We found that the prevalence of migraine in patients with IBD is significantly more than normal population. More studies are needed to highlight the correlation between migraine and IBD.
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Affiliation(s)
- Somaye Chehel Cheraghi
- Internal Medicine Resident, Gastroenterology Department, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mojdeh Ghabaee
- Associate Professor, Neurology Department, Tehran University of Medical Sciences, Tehran, Iran
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44
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Raymond SB, Gee MS, Anupindi SA, Shailam R, Kaplan JL, Nimkin K. CT and MRI of Rare Extraintestinal Manifestations of Inflammatory Bowel Disease in Children and Adolescents. J Pediatr Gastroenterol Nutr 2016; 63:e1-9. [PMID: 27050046 DOI: 10.1097/mpg.0000000000001225] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Inflammatory bowel disease (IBD) is associated with a spectrum of extraintestinal manifestations (EIMs) affecting many organ systems. EIMs can occur in more than 40% of patients with IBD and are associated with significant morbidity. They occur at any time point in the course of disease, often during an active phase of bowel inflammation, but sometimes preceding bowel disease. Prompt recognition of EIMs enables timely and more effective therapy. Physicians who image patients with IBD should be aware of the myriad extraintestinal conditions that may be detected on imaging studies, both within and outside of the abdomen, as they may predate the diagnosis of IBD. Cross-sectional imaging of unusual conditions associated with IBD will be presented, including pathology in the hepatobiliary, pancreatic, genitourinary, musculoskeletal, mucocutaneous, vascular, neurologic, and pulmonary systems.
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Affiliation(s)
- Scott B Raymond
- *Department of Radiology†Department of Radiology, Division of Pediatric Radiology, Massachusetts General Hospital, Boston, MA‡Department of Radiology, The Children's Hospital of Philadelphia, Philadelphia, PA§Department of Pediatrics, Division of Pediatric Gastroenterology, MassGeneral Hospital for Children, Boston, MA
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45
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Chronic Inflammatory Demyelinating Polyneuropathy Following Anti-TNF-α Therapy With Infliximab for Crohn's Disease. ACG Case Rep J 2016; 3:187-9. [PMID: 27144200 PMCID: PMC4843152 DOI: 10.14309/crj.2016.45] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Accepted: 08/25/2015] [Indexed: 12/16/2022] Open
Abstract
We present a 29-year-old male with Crohn's disease who developed chronic inflammatory demyelinating polyneuropathy (CIDP) related to infliximab therapy. He developed lower extremity weakness and dysesthesia 3 weeks after a fourth infliximab dose. Laboratory examination revealed an elevated cerebrospinal fluid protein without pleocytosis. The patient initially responded to plasmapheresis therapy with marked symptomatic improvement, but relapsed and was refractory to subsequent treatments with plasmaphereisis, intravenous immunoglobulin, and glucocorticoids. While a causal relationship between infliximab and CIDP cannot be proven, clinicians should monitor Crohn's disease patients who are receiving TNF-α antagonists for neurologic symptoms suggestive of demyelinating disease.
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46
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The Prevalence of Headache in Crohn's Disease: Single-Center Experience. Gastroenterol Res Pract 2016; 2016:6474651. [PMID: 26904110 PMCID: PMC4745315 DOI: 10.1155/2016/6474651] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 12/30/2015] [Indexed: 12/22/2022] Open
Abstract
Objectives. This study is aimed at studying the prevalence and characteristics of different types of headaches in patients with Crohn's disease. Materials and Methods. 51 patients in Crohn's disease group (F/M: 26/25) and 51 patients in control group (F/M: 27/24) were involved. Patients in Crohn's disease group were diagnosed and monitored according to European Crohn's and Colitis Organization diagnostic criteria. The control group composed of healthy subjects with similar age and sex to Crohn's disease group. Headache was classified using the International Headache Society II criteria. Results. Headache was reported by 35/51 (68.6%) patients in Crohn's disease group and 21/51 (41.2%) patients in the control group. The prevalence of headache was statistically high in the group with Crohn's disease (OR: 3.125 (95% CI: 1.38-7.04); p = 0.01). Comparing two groups with respect to their subtypes of headaches resulted in that the tension-type headache was statistically (p = 0.008) higher in Crohn's disease group (26/51) than in the control group (12/51). However, no significant difference was found in the migraine-type headache (p = 1). Conclusions. This study indicates that the prevalence of headache is high in patients with Crohn's disease and most commonly associated with the tension-type headache.
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47
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Selvitop O, Poretti A, Huisman TA, Wagner MW. Cerebral sinovenous thrombosis in a child with Crohn's disease, otitis media, and meningitis. Neuroradiol J 2015; 28:274-7. [PMID: 26246095 DOI: 10.1177/1971400915589688] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Pediatric cerebral sinovenous thrombosis (CSVT) is associated with high morbidity and mortality. Severe long-term sequelae are reported in up to 48% of children. The most frequent location of CSVT in children is the superficial venous system. We present the neuroimaging findings using both computed tomography and magnetic resonance imaging (MRI) in a 10-year-old child with extensive superficial CSVT. Our report aims to stress the importance of awareness of risk factors in suspecting and rapidly diagnosing CSVT. The application of targeted conventional and advanced MRI sequences is the diagnostic tool of choice in children at risk of or with clinically suspected CSVT.
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Affiliation(s)
- Omer Selvitop
- Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Andrea Poretti
- Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Thierry Agm Huisman
- Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Matthias W Wagner
- Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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48
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A Case of Cerebral Vasculitis Associated with Ulcerative Colitis. Case Rep Rheumatol 2015; 2015:598273. [PMID: 26557402 PMCID: PMC4628684 DOI: 10.1155/2015/598273] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 09/29/2015] [Accepted: 10/05/2015] [Indexed: 11/20/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic, debilitating condition characterized by inflammation of the colonic mucosa. It is regarded as a systemic inflammatory disorder that can affect a number of organ systems. Central nervous system disease associated with UC is a rare sequela of inflammatory bowel disease, occurring in less than 5% of cases. These manifestations include arterial and venous thrombosis, leukoencephalitis, seizures, and vasculitis. We present a case of a 61-year-old female with a two-year history of well-controlled ulcerative colitis, who developed altered mental status and weakness. On brain imaging, she was found to have cerebral lesions which were biopsied. Histopathology subsequently revealed coagulative necrosis and inflammation characteristic of vasculitis. Rheumatology serologies were negative, and the patient was started on steroids that dramatically improved her neurological function, with no residual deficits, and led to resolution of the brain lesions.
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49
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Gekka M, Sugiyama T, Nomura M, Kato Y, Nishihara H, Asaoka K. Histologically confirmed case of cerebral vasculitis associated with Crohn's disease--a case report. BMC Neurol 2015; 15:169. [PMID: 26390922 PMCID: PMC4578610 DOI: 10.1186/s12883-015-0429-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 09/14/2015] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Extraintestinal manifestations in Crohn's disease (CD) are frequent and well recognized. However, neurological involvement secondary to CD is rare, and there have been few histologically confirmed cases of cerebral vasculitis secondary to CD. CASE PRESENTATION A 58-year-old left-handed man with a history of refractory CD who had fever of over 38 °C, progression of CD symptoms, and Gerstmann's syndrome consulted our hospital. Laboratory data showed elevation of C-reactive protein (CRP) and hypoproteinemia. T2-weighted magnetic resonance imaging (MRI) revealed a right parietal high-intensity lesion. Catheter angiography showed segmental multiple narrowing and occlusion in the distal part of the middle cerebral artery and anterior cerebral artery. Angiography also revealed multiple venous occlusions in the affected parietal area. To confirm the diagnosis, the patient underwent open biopsy, and histological examination revealed cerebral vasculitis. The patient was then started on high-dose prednisolone (60 mg/day) in addition to his previous therapy, which included mesalazine, adalimumab, and azathioprine. CRP elevation, hypoproteinemia, and gastrointestinal symptoms immediately improved after starting this treatment. Neurological status improved simultaneously with CD symptom improvement, and follow-up brain MRI revealed a reduction in the size of the right parietal lobe lesion. He returned to normal status and was discharged from our hospital 5 weeks after admission. CONCLUSION This is an important case of histologically confirmed cerebral vasculitis associated with CD. The clinical course of our case clearly illustrates the relevance of the occurrence of cerebral vasculitis and the exacerbation of CD.
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Affiliation(s)
- Masayuki Gekka
- Department of Neurosurgery, Teine Keijinkai Medical Center, 1-40 Maeda 1-12, Teine-Ku, Sapporo, 006-8555, Japan.
| | - Taku Sugiyama
- Department of Neurosurgery, Teine Keijinkai Medical Center, 1-40 Maeda 1-12, Teine-Ku, Sapporo, 006-8555, Japan.
| | - Masafumi Nomura
- Center for Gastroenterology, Teine Keijinkai Medical Center, 1-40 Maeda 1-12, Teine-Ku, Sapporo, 006-8555, Japan.
| | - Yasutaka Kato
- Department of Translational Pathology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
| | - Hiroshi Nishihara
- Department of Translational Pathology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
| | - Katsuyuki Asaoka
- Department of Neurosurgery, Teine Keijinkai Medical Center, 1-40 Maeda 1-12, Teine-Ku, Sapporo, 006-8555, Japan.
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50
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Clinical and Electrodiagnostic Findings in Patients with Peripheral Neuropathy and Inflammatory Bowel Disease. Inflamm Bowel Dis 2015; 21:2123-9. [PMID: 25993692 DOI: 10.1097/mib.0000000000000459] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Several neurological diseases, especially different types of peripheral neuropathy (PN) are common in inflammatory bowel disease (IBD). METHODS We prospectively evaluated the presence of PN in 121 patients with IBD (51 with Crohn's disease [CD] and 70 with ulcerative colitis [UC]) and 50 controls (gastritis and dyspepsia) over 3.5 years. RESULTS A total of 15 patients (12.4%) with small-fiber neuropathy and IBD (7 CD and 8 UC) and 24 patients (19.8%) with large-fiber PN (12 CD and 12 UC) were diagnosed. Small-fiber neuropathy affected 6% and large-fiber PN affected 4% of the control patients. Patients with CD with PN were older, had more metabolic complications and more severe motor involvement than patients with UC with PN. Carpal tunnel syndrome was more common in patients with UC. Sural and median sensory nerves were the most commonly and severely affected sensory responses. Tibial, peroneal, median, and ulnar compound muscle action potential amplitudes were also significantly decreased in patients with CD and UC. In general, sensory and motor amplitudes were a more sensitive marker for PN in patients with IBD than conduction velocities. CONCLUSIONS In summary, PN is common in patients with IBD. It may be primarily related to IBD, phenotypically modified by metabolic complications. Its phenotype is diverse (most commonly small to predominantly axonal sensory large-fiber), but usually more severe in CD. It also includes ataxic and demyelinating forms. Results from our 10-year follow-up will elucidate the PN clinical course and the real impact of the comorbidities and new therapies.
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