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Huang J, Yang J, Zou X, Zuo S, Wang J, Cheng J, Zhu H, Li W, Shi M, Zhao G, Liu Z. Ginkgolide B promotes oligodendrocyte precursor cell differentiation and survival via Akt/CREB/bcl-2 signaling pathway after white matter lesion. Exp Biol Med (Maywood) 2021; 246:1198-1209. [PMID: 33557607 PMCID: PMC8142115 DOI: 10.1177/1535370221989955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 01/03/2021] [Indexed: 12/12/2022] Open
Abstract
White matter lesion (WML) is caused by chronic cerebral hypoperfusion, which are usually associated with cognitive impairment. Evidence from recent studies has shown that ginkgolide B has a neuroprotective effect that could be beneficial for the treatment of ischemia; however, it is not clear whether ginkgolide B has a protective effect on WML. Our data show that ginkgolide B can promote the differentiation of oligodendrocyte precursor cell (OPC) into oligodendrocytes and promote oligodendrocyte survival following a WML. Ginkgolide B (5, 10, 20 mg/kg) or saline is administered intraperitoneally every day after WML. After 4 weeks, the data of Morris water maze suggested that rats' memory and learning abilities were impaired, and the administration of ginkgolide B enhanced behavioral achievement. Also, treatment with ginkgolide B significantly attenuated this loss of myelin. Our result suggests that ginkgolide B promotes the differentiation of OPC into oligodendrocytes. We also found that ginkgolide B ameliorates oligodendrocytes apoptosis. Furthermore, ginkgolide B enhanced the expression of phosphorylated Akt and CREB. In conclusion, our data firstly show that ginkgolide B promotes oligodendrocyte genesis and oligodendrocyte myelin following a WML, possibly involving the Akt and CREB pathways.
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Affiliation(s)
- Jian Huang
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Jun Yang
- Department of Nephrology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Xingju Zou
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Shilun Zuo
- Department of Neurology, Second Affiliated Hospital of Army Military Medical University, Chongqing 400038, China
| | - Jing Wang
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Jing Cheng
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Hao Zhu
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Weiwang Li
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Ming Shi
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Gang Zhao
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
| | - Zhirong Liu
- Department of Neurology, Xijing Hospital, Airforce Military Medical University, Xi'an, Shaanxi 710032, China
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Dziadkowiec KN, Stawinski P, Radadiya D, Al Abbasi B, Isaac S. Is Multiple Sclerosis an Extra-Intestinal Manifestation of Inflammatory Bowel Disease? Food for Thought. Cureus 2020; 12:e9485. [PMID: 32874812 PMCID: PMC7455465 DOI: 10.7759/cureus.9485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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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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4
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Camara-Lemarroy CR, Metz L, Meddings JB, Sharkey KA, Wee Yong V. The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics. Brain 2019; 141:1900-1916. [PMID: 29860380 DOI: 10.1093/brain/awy131] [Citation(s) in RCA: 134] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 03/24/2018] [Indexed: 12/12/2022] Open
Abstract
Biological barriers are essential for the maintenance of homeostasis in health and disease. Breakdown of the intestinal barrier is an essential aspect of the pathophysiology of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. A wealth of recent studies has shown that the intestinal microbiome, part of the brain-gut axis, could play a role in the pathophysiology of multiple sclerosis. However, an essential component of this axis, the intestinal barrier, has received much less attention. In this review, we describe the intestinal barrier as the physical and functional zone of interaction between the luminal microbiome and the host. Besides its essential role in the regulation of homeostatic processes, the intestinal barrier contains the gut mucosal immune system, a guardian of the integrity of the intestinal tract and the whole organism. Gastrointestinal disorders with intestinal barrier breakdown show evidence of CNS demyelination, and content of the intestinal microbiome entering into the circulation can impact the functions of CNS microglia. We highlight currently available studies suggesting that there is intestinal barrier dysfunction in multiple sclerosis. Finally, we address the mechanisms by which commonly used disease-modifying drugs in multiple sclerosis could alter the intestinal barrier and the microbiome, and we discuss the potential of barrier-stabilizing strategies, including probiotics and stabilization of tight junctions, as novel therapeutic avenues in multiple sclerosis.
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Affiliation(s)
- Carlos R Camara-Lemarroy
- Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Luanne Metz
- Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Jonathan B Meddings
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Keith A Sharkey
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - V Wee Yong
- Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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5
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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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Pollak L, Osherov M, Berkovitz N, Beckerman I, Stryjer R, Tal S. Magnetic resonance brain imaging in patients with visual vertigo. Brain Behav 2015; 5:e00402. [PMID: 26664788 PMCID: PMC4667762 DOI: 10.1002/brb3.402] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2015] [Revised: 08/22/2015] [Accepted: 09/02/2015] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION Patients with visual vertigo (VV) report dizziness provoked by moving visual surroundings. It has been suggested that these subjects develop a compensation strategy for a vestibulo-proprioceptive deficit and rely excessively on visual input. We have postulated that patients with VV might have brain abnormalities that interfere with appropriate processing of visual stimulation and performed a brain MRI study to verify this hypothesis. MATERIALS AND METHODS Patients with VV of more than 3 months duration were included. They were asked to complete the Situational Characteristic Questionnaire (SCQ) that scores for the symptoms of VV. Dizzy patients without VV served as controls. A brain MRI was performed with a Siemens 1.5 Tesla scanner in patients and controls. RESULTS Twenty-four patients with VV were included. Their mean SCQ score was 1.45 ± 0.9 (normal 0.16 ± 0.28). In 50% of patients, abnormalities in MRI imaging were found. Thirty-three percent of 27 controls demonstrated an abnormal brain MRI. The two groups were similar in respect to the prevalence of a localized hemispheric or posterior fossa lesion (P = 0.13), but VV patients had more unspecific white matter brain changes than controls (P = 0.009). Patients and controls did not differ in age and gender distribution (P = 0.9) or the history of a neurotological event preceding their symptoms (P = 0.3). CONCLUSIONS Our study suggests that multiple white matter lesions might contribute to occurrence of the phenomenon of VV. Future prospective large-scale studies by specific MR techniques are indicated to validate our preliminary findings and elucidate the pathological mechanism of VV.
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Affiliation(s)
- Lea Pollak
- Department of Neurology The Assaf Harofeh Medical Center Zerifin Israel ; Affiliated to The Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - Michael Osherov
- Department of Neurology The Assaf Harofeh Medical Center Zerifin Israel ; Affiliated to The Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - Nadav Berkovitz
- Affiliated to The Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel ; Department of Radiology The Assaf Harofeh Medical Center Zerifin Israel
| | - Inessa Beckerman
- Affiliated to The Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel ; Department of Radiology The Assaf Harofeh Medical Center Zerifin Israel
| | - Rafael Stryjer
- Affiliated to The Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel ; Public Health Hospital Beer Yaacov Israel
| | - Sigal Tal
- Affiliated to The Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel ; Department of Radiology The Assaf Harofeh Medical Center Zerifin Israel
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7
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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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Gharedaghi MH, Rahimian R, Dehpour AR, Yousefzadeh-Fard Y, Mohammadi-Farani A. Dinitrobenzene sulphonic acid-induced colitis impairs spatial recognition memory in mice: roles of N-methyl D-aspartate receptors and nitric oxide. Psychopharmacology (Berl) 2015; 232:3081-90. [PMID: 25971874 DOI: 10.1007/s00213-015-3950-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2014] [Accepted: 04/22/2015] [Indexed: 12/21/2022]
Abstract
RATIONALE Many peripheral diseases are associated with a decline in cognitive function. In this regard, there have been reports of patients with inflammatory bowel disease and an otherwise unexplained memory impairment. OBJECTIVES We sought to assess the memory performance of mice with colitis. We also investigated the roles of N-methyl D-aspartate (NMDA) receptors and nitric oxide (NO) as possible mediators of colitis-induced amnesia. METHODS To induce colitis, male NMRI mice were intrarectally injected with a solution containing dinitrobenzene sulfonic acid (DNBS; 4 mg in 100 μl) under anesthesia. Three days after intrarectal DNBS instillation, spatial recognition and associative memories were assessed by the Y-maze and passive avoidance tasks, respectively. The NMDA antagonists, MK-801 and memantine, and the inducible NO synthase (iNOS) inhibitor, aminoguanidine, were injected intraperitoneally 45 min before the Y-maze task. RESULTS Induction of colitis by DNBS impaired spatial recognition memory in the Y-maze task but had no effect on step through latencies in the passive avoidance test. Colitis-induced amnesia was reversed by administering specific doses of MK-801 and memantine (30 μg/kg and 1 mg/kg, respectively) suggesting dysregulated NMDA receptor activation as an underlying mechanism. No effect was seen with lower and higher doses of these drugs, resulting in a bell-shaped dose response curve. Colitis-induced amnesia was also inhibited by aminoguanidine (50 mg/kg), implicating a role for iNOS activation and neuroinflammation in this phenomenon. CONCLUSION DNBS-induced colitis impairs memory through NMDA receptor overstimulation and NO overproduction.
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Affiliation(s)
- Mohammad Hadi Gharedaghi
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran
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9
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Casella G, Tontini GE, Bassotti G, Pastorelli L, Villanacci V, Spina L, Baldini V, Vecchi M. Neurological disorders and inflammatory bowel diseases. World J Gastroenterol 2014; 20:8764-8782. [PMID: 25083051 PMCID: PMC4112885 DOI: 10.3748/wjg.v20.i27.8764] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 02/14/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.
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10
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Morís G. Inflammatory bowel disease: An increased risk factor for neurologic complications. World J Gastroenterol 2014; 20:1228-1237. [PMID: 24574797 PMCID: PMC3921505 DOI: 10.3748/wjg.v20.i5.1228] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Revised: 12/21/2013] [Accepted: 01/05/2014] [Indexed: 02/06/2023] Open
Abstract
Only a very few systematic studies have investigated the frequency of neurologic disorders in patients with Crohn’s disease (CD) and ulcerative colitis (UC), which are the two main types of inflammatory bowel disease (IBD). Results have been inconsistent and variable, owing to differences in case-finding methods and evaluated outcomes in different studies. The most frequent neurologic manifestations reported in CD and UC populations are cerebrovascular disease (with either arterial or venous events), demyelinating central nervous system disease, and peripheral neuropathy (whether axonal or demyelinating); however, the literature describes numerous nervous system disorders as being associated with IBD. The pathogenesis of nervous system tissue involvement in IBD has yet to be elucidated, although it seems to be related to immune mechanisms or prothrombotic states. The recently-introduced tumor necrosis factor (TNF) inhibitors have proven successful in controlling moderate to severe IBD activity. However, severe neurologic disorders associated with TNF inhibitors have been reported, which therefore raises concerns regarding the effect of anti-TNF-α antibodies on the nervous system. Although neurological involvement associated with IBD is rarely reported, gastroenterologists should be aware of the neurologic manifestations of IBD in order to provide early treatment, which is crucial for preventing major neurologic morbidity.
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11
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Pfeiffer RF. Other Neurologic Disorders Associated with Gastrointestinal Disease. AMINOFF'S NEUROLOGY AND GENERAL MEDICINE 2014:237-253. [DOI: 10.1016/b978-0-12-407710-2.00013-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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12
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Ferretti A, Parisi P, Villa MP. The role of hyperhomocysteinemia in neurological features associated with coeliac disease. Med Hypotheses 2013; 81:524-31. [PMID: 23891042 DOI: 10.1016/j.mehy.2013.06.025] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2013] [Revised: 06/15/2013] [Accepted: 06/22/2013] [Indexed: 12/14/2022]
Abstract
Although a range of neurological and psychiatric disorders are widely reported to be associated with coeliac patients, their pathogenesis remains unclear. Some such disorders are believed to be secondary to vitamin deficiency due to malabsorption, others to immune mechanisms. We hypothesise that hyperhomocysteinemia might, by damaging the blood-brain barrier, expose neuronal tissue to all neuro-irritative metabolites, such as homocysteine itself, a neurotoxic excitatory and proconvulsant amino acid. Neurons respond to these stimuli through hyperexcitability, thereby predisposing subjects to neurological disorders such as epilepsy and headache. Furthermore, persisting endothelial damage may cause blood extravasation and subsequent deposition of calcium salts. We suggest that this might be the pathogenesis of the CEC syndrome, which is characterized by the association of coeliac disease, epilepsy and cerebral calcifications. Indeed, homocysteine plays a well-known role in cardiovascular endothelial dysfunction, with high serum and cerebrospinal fluid levels often being reported in coeliac patients. Moreover, data in the literature show a strong, growing association of homocysteine with epilepsy and migraine in non-coeliac subjects. Despite these findings, homocysteine has never been held directly responsible for neuronal functional features (neuronal hyperexcitability underlying epilepsy and migraine) and structural brain damage (expressed as cerebral calcification) in coeliac patients. Damage to the blood-brain barrier might also facilitate immune reactions against neuronal tissue to a considerable extent. This hypothesis combines the two afore-mentioned theories (vitamin deficiency due to malabsorption and immune mechanisms). We also wish to point out that no studies have yet investigated the prevalence of neuronal hyperexcitability and subclinical electroencephalic abnormalities in children and adults with newly-diagnosed coeliac disease before the introduction of a gluten-free diet, and in particular any changes following the introduction of the diet. We believe that the onset of clinical symptoms such as migraine and convulsions is preceded by a period in which damage is expressed exclusively by subclinical electroencephalic abnormalities; persisting damage to neuronal tissue subsequently leads to clinical manifestations. We propose two types of investigations: the first is to determine whether newly-diagnosed coeliac patients with hyperhomocysteinemia are a subgroup at risk for neurological features (clinical and subclinical); the second is to determine whether appropriate treatment of hyperhomocysteinemia and vitamin B status deficiency improves neurological abnormalities and reduces the risk of cerebral calcifications. The aim of these investigations is to develop new therapeutic strategies designed to prevent neuronal damage and increase the quality of life in children affected by such disorders.
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Affiliation(s)
- Alessandro Ferretti
- Pediatric Sleep Disease Centre, Child Neurology, NESMOS Department, School of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, Via di Grottarossa 1035-39, 00189 Rome, Italy
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13
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Dolapcioglu C, Guleryuzlu Y, Uygur-Bayramicli O, Ahishali E, Dabak R. Asymptomatic brain lesions on cranial magnetic resonance imaging in inflammatory bowel disease. Gut Liver 2013; 7:169-74. [PMID: 23560152 PMCID: PMC3607770 DOI: 10.5009/gnl.2013.7.2.169] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2011] [Revised: 05/16/2012] [Accepted: 06/15/2012] [Indexed: 12/26/2022] Open
Abstract
Background/Aims This study aimed to examine the frequency and type of asymptomatic neurological involvement in inflammatory bowel disease (IBD) using cranial magnetic resonance imaging (MRI). Methods Fifty-one IBD patients with no known neurological diseases or symptoms and 30 controls with unspecified headaches without neurological origins were included. Patients and controls underwent cranial MRI assessments for white matter lesions, sinusitis, otitis-mastoiditis, and other brain parenchymal findings. Results The frequencies of white matter lesions, other brainstem parenchymal lesions, and otitis-mastoiditis were similar in IBD patients and controls (p>0.05), whereas sinusitis was significantly more frequent in IBD patients (56.9% vs 33.3%, p=0.041). However, among those subjects with white matter lesions, the number of such lesions was significantly higher in IBD patients compared to controls (12.75±9.78 vs 3.20±2.90, p<0.05). The incidence of examined pathologies did not differ significantly with disease activity (p>0.05 for all). Conclusions The incidence of white matter lesions seemed to be similar in IBD patients and normal healthy individuals, and the lesions detected did not pose any clinical significance. However, long-term clinical follow-up of the lesions is warranted.
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Affiliation(s)
- Can Dolapcioglu
- Department of Gastroenterology, Dr. Lutfi Kirdar Kartal Research and Training Hospital, Istanbul, Turkey
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14
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Ho BL, Yu FJ, Lai CL, Lin HH. Avellis syndrome as presenting manifestation of ulcerative colitis. J Neurol Sci 2013; 325:160-1. [DOI: 10.1016/j.jns.2012.11.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2012] [Revised: 11/12/2012] [Accepted: 11/27/2012] [Indexed: 11/29/2022]
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Banati M, Csecsei P, Koszegi E, Nielsen HH, Suto G, Bors L, Trauninger A, Csepany T, Rozsa C, Jakab G, Molnar T, Berthele A, Kalluri SR, Berki T, Illes Z. Antibody response against gastrointestinal antigens in demyelinating diseases of the central nervous system. Eur J Neurol 2013; 20:1492-5. [PMID: 23293933 DOI: 10.1111/ene.12072] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Accepted: 11/07/2012] [Indexed: 01/29/2023]
Abstract
BACKGROUND Antibodies against gastrointestinal antigens may indicate altered microbiota and immune responses in the gut. Recent experimental data suggest a connection between gastrointestinal immune responses and CNS autoimmunity. METHODS Antibodies against gliadin, tissue transglutaminase (tTG), intrinsic factor (IF), parietal cells (PC) and Saccharomyces cerevisiae (ASCA) were screened in the sera of 45 patients with AQP4-seropositive neuromyelitis optica (NMO) and NMO spectrum diseases (NMO/NMO-SD), 17 patients with AQP4-seronegative NMO, 85 patients with clinically definite multiple sclerosis (MS), and 48 healthy controls (HC). RESULTS Thirty-seven percentages of patients with AQP4-seropositive NMO/NMO-SD and 28% of patients with MS had at least one particular antibody in contrast to 8% of HC (P < 0.01, respectively). Antibodies were most common (46%) in AQP4-seropositive myelitis (P = 0.01 versus HS, P = 0.05 versus MS). Anti-gliadin and ASCA were more frequent in the AQP4-seropositive NMO-spectrum compared to controls (P = 0.01 and P < 0.05, respectively). CONCLUSION Antibody responses against gastrointestinal antigens are common in MS and AQP4-seropositive NMO/NMO-SD, especially in longitudinally extensive myelitis.
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Affiliation(s)
- M Banati
- Department of Neurology, University of Pecs, Pecs, Hungary
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Alkhawajah MM, Caminero AB, Freeman HJ, Oger JJF. Multiple sclerosis and inflammatory bowel diseases: what we know and what we would need to know! Mult Scler 2012; 19:259-65. [PMID: 23027881 DOI: 10.1177/1352458512461393] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS) but the causes have not been defined. The disease process appears to involve interplay between environmental factors and certain susceptibility genes. It is likely that the identification of the exact etiological mechanisms will permit the development of preventive and curative treatments. Evaluation of several diseases found to be more often associated than by chance alone may reveal clues to the etiology of those disorders. An association between MS and inflammatory bowel diseases (IBD) was suggested by the observation of an increased incidence of IBD among MS patients. A problem in the interpretation of the data rests, in part, with the observation that abnormal findings in brain magnetic resonance imaging (MRI) may be reported as MS in IBD patients. Defining the limits between incidental MRI findings and findings compatible with MS has resulted in further exploration of this possible association.
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Affiliation(s)
- Mona M Alkhawajah
- Multiple Sclerosis Clinic, University of British Columbia Hospital, Canada.
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Zhang XJ, Leung FP, Hsiao WWL, Tan S, Li S, Xu HX, Sung JJY, Bian ZX. Proteome profiling of spinal cord and dorsal root ganglia in rats with trinitrobenzene sulfonic acid-induced colitis. World J Gastroenterol 2012; 18:2914-28. [PMID: 22736915 PMCID: PMC3380319 DOI: 10.3748/wjg.v18.i23.2914] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2011] [Revised: 09/24/2011] [Accepted: 04/12/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate proteomic changes in spinal cord and dorsal root ganglia (DRG) of rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis.
METHODS: The colonic myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) level were determined. A two-dimensional electrophoresis (2-DE)-based proteomic technique was used to profile the global protein expression changes in the DRG and spinal cord of the rats with acute colitis induced by intra-colonic injection of TNBS.
RESULTS: TNBS group showed significantly elevated colonic MPO activity and increased TNF-α level. The proteins derived from lumbosacral enlargement of the spinal cord and DRG were resolved by 2-DE; and 26 and 19 proteins that displayed significantly different expression levels in the DRG and spinal cord were identified respectively. Altered proteins were found to be involved in a number of biological functions, such as inflammation/immunity, cell signaling, redox regulation, sulfate transport and cellular metabolism. The overexpression of the protein similar to potassium channel tetramerisation domain containing protein 12 (Kctd 12) and low expression of proteasome subunit α type-1 (psma) were validated by Western blotting analysis.
CONCLUSION: TNBS-induced colitis has a profound impact on protein profiling in the nervous system. This result helps understand the neurological pathogenesis of inflammatory bowel disease.
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Abstract
BACKGROUND AND PURPOSE the study is aimed to report neurologic manifestations in a population of patients with inflammatory bowel disease in order to address its clinical characteristics. METHODS we conducted a retrospective study based on a computer-guided search, of patients with Crohn's disease or ulcerative colitis diagnosed at three hospitals in Spain spanning from 2000 through 2008. Patients were classified into different clinical groups based on the type of neurologic involvement. Only patients without iatrogenic complications, vitamin deficiencies, or known cerebrovascular risk factors were included. RESULTS we identified and reviewed the records of eighty-four inflammatory bowel disease patients with neurologic symptoms: thirteen patients with ulcerative colitis and twelve patients with Crohn's disease associated with neurologic complications were identified. Their ages ranged from 17 to 74 years. There was a slight predominance of women. Only four of them have another extra-intestinal manifestation. Most of the patients developed neurologic manifestations coincidental or after digestive symptoms appeared. Demyelinating disease was the most frequent manifestation observed (8 patients). Cerebrovascular, peripheral nerve, and epilepsy disorders were diagnosed in 6, 5, and 3 patients, respectively. One patient with myoclonus, one with amyotrophic lateral sclerosis, and one with sensorineural hearing loss were found. CONCLUSIONS although an incidence could not be obtained, this population of patients with inflammatory bowel disease have a low frequency of severe neurologic disorders. Neurologic diseases, such as cerebrovascular disease, demyelinating disease, and peripheral neuropathy, could be associated with Crohn's disease and ulcerative colitis.
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Affiliation(s)
- L Benavente
- Neurology Department, Hospital Universitario Central Asturias, Oviedo Neurology Service, Hospital San Agustín, Avilés, Asturias, Spain
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Lionetti E, Francavilla R, Pavone P, Pavone L, Francavilla T, Pulvirenti A, Giugno R, Ruggieri M. The neurology of coeliac disease in childhood: what is the evidence? A systematic review and meta-analysis. Dev Med Child Neurol 2010; 52:700-7. [PMID: 20345955 DOI: 10.1111/j.1469-8749.2010.03647.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
AIM The aim of this article was to review and conduct a meta-analysis of the paediatric literature on the neurology of coeliac disease. METHOD We conducted a review of paediatric studies published in English assessing neurological illness in coeliac disease identified through a MEDLINE search (1950-2009). Calculation of computed relative risk, odds ratio, and risk difference was performed using the fixed effect method if applicable. RESULTS Fifteen studies were analysed (11 772 participants). The meta-analysis showed that (1) the relative risk of epilepsy in individuals with coeliac disease, and of coeliac disease in individuals with epilepsy, compared with the general population, was 2.1 and 1.7, respectively, and the risk difference was close to zero, indicating that it was probably a chance association; and (2) the relative risk of headache in individuals with the disease compared with comparison groups was 3.2. In two studies, cerebellar ataxia was documented in 2.7 to 5.4% of participants; in two further studies, the risk of cerebellar dysfunction was zero. Two studies found an association between coeliac disease and peripheral neuropathy. Brain white matter lesions were recorded in two other studies. An association between autism and coeliac disease is disputed. Interpretation Children with coeliac disease are at risk of developing neurological complications, but the risk is lower than in adulthood. The discrepancy might be due to short disease duration, early elimination of gluten from the diet, stricter adherence to diet, or different susceptibility to immune-mediated disorders.
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Affiliation(s)
- Elena Lionetti
- Department of Pediatrics, University of Catania, Catania, Italy.
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