Neurologic Sequelae of Inflammatory Bowel Disease
April 1, 2008 3 minutes read
Neurologic Sequelae of Inflammatory Bowel Disease
Abstract & Commentary
By Michael Rubin, MD, FRCP(C) Professor of Clinical Neurology, Weill Cornell Medical College, New York, NY Dr. Rubin reports that he is involved with grant/research support for Pfizer and is on the speaker's bureau for Athena Diagnostics.
Synopsis: Neuropathic symptoms and signs occur in about one-half of patients with inflammatory bowel disease.
Source: Oliveira GR, et al. Peripheral neuropathy and neurological disorders in an unselected Brazilian population-based cohort of IBD patients. Inflamm Bowel Dis 2008;14:389-395.
Inflammatory bowel disease (IBD), characterized predominantly by Crohn's disease and ulcerative colitis, is of presumed autoimmune origin and manifests multiple extra-intestinal complications, including iritis, episcleritis, arthritis, skin involvement, pericholangitis, and sclerosing cholangitis. Neurologic complications with IBD are reported but their frequency is unknown.
A prospective study of 31 patients with Crohn's disease and 51 patients with ulcerative colitis, seen at the IBD Clinic of the Hospital Universitaro Walter Candidio and General Gastroenterology Clinic of the Hospital Cesar Cals in Brazil, was undertaken to determine the form and frequency of neurologic disorders associated with IBD. Diagnosis of IBD was confirmed by clinical, endoscopic, radiologic, and pathologic criteria. Patients were followed for 1 year and underwent neurologic examination by 2 independent neurologists, extensive blood testing including complete blood count, sedimentation rate, glucose tolerance testing, antinuclear antibodies, rheumatoid factor, thyroid function, B12, folate, serum protein electrophoresis, hepatitis and HIV testing, electrodiagnostic studies, and where indicated, quantitative sensory testing, neuroimaging, visual and somatosensory evoked response studies, and electroencephalogram. Statistical analysis encompassed chi-square, Mann-Whitney, and t-tests and p < 0.05 was considered significant.
Headache was the most common complaint, reported in 54.8% and 56.9% of Crohn's disease and ulcerative colitis patients, respectively; it usually was associated with IBD flare or treatment alteration. Migraine headache criteria were satisfied in 25% of both groups. Bell's palsy or ischemic stroke were each seen in 3, epilepsy in 5, and transient chorea in 1. Neuromuscular complications affected 51.6% and 45.1% of patients, respectively, and were more commonly seen in women than men. Myopathy and neuromuscular junctionopathy did not occur. Mild carpal tunnel syndrome was common among women with ulcerative colitis. Large fiber sensory or sensorimotor polyneuropathy was documented in 16.1% and 19.6% of patients, respectively, whereas sensory symptoms suggestive of small fiber neuropathy or myelopathy, in the absence of confirmatory electrodiagnostic evidence, was present in 29% and 11.85%, respectively. Overall, 13.3% of IBD patients had polyneuropathy that could not be ascribed to other causes. Neurological complications in IBD are common and usually mild, but deserve attention in the overall care of such patients.
Commentary
Nutrients, bacteria, and viruses constantly bombard the gastrointestinal (GI) tract and the GI mucosa must decide what to absorb and what to reject. An innate GI immune system exists to assist in this task and its malfunction may contribute to GI inflammation. Recent progress has been made in understanding how the enteric immune system works.1
Toll-like receptors (TLRs), expressed by a variety of GI mucosal cells, comprise at least 12 transmembrane pattern recognition receptors (PRRs) that recognize molecular patterns present on luminal antigens. TLRs also participate in inducing antimicrobial effector pathways and in controlling adaptive immune responses, thereby providing effective homeostasis of the GI mucosa. While in the healthy host TLRs protect barrier integrity, in the susceptible host TLRs may induce overactive signaling pathways, leading to an inappropriate immune response that results in chronic inflammation and tissue injury. These mechanisms suggest that therapy directed at TLR-based targets may be beneficial in treating IBD and in preventing the neurological complications that result.
Reference
1. Cario E. Therapeutic impact of toll-like receptors on inflammatory bowel diseases: a multiple-edged sword. Inflamm Bowel Dis 2008;14:411-421.
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