Weiser_edit.qxp 10/4/08 03:04 Page 70
Irritable Bowel Syndrome
Evolving Issues in the Diagnosis, Evaluation, and Management of
Irritable Bowel Syndrome
a report by
Kirsten T Weiser, MD, Abigail T Kennedy, BA and Brian E Lacy, MD, PhD
Division of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal motility The first IBS imaging study used PET to investigate the brain’s response to
disorder associated with decreased quality of life
1
and significant economic painful visceral stimuli, namely rectal distention. Altered levels of
burden to both the individual patient and society.
2
For these reasons IBS has activation of various brain regions were noted in IBS patients relative to
remained an area of active clinical research. This article will provide a controls.
5
Later studies employed fMRI or MEG, and tested neural
summary of recent changes in the Rome criteria, discuss how brain imaging responses to sham, subliminal, and non-painful rectal distension, as well
broadens our understanding of the brain–gut axis in IBS, and review new as auditory and heterotopic stimuli. For example, a study by Andresen and
data on serotonergic agents, bacterial overgrowth, probiotics, and IBS. colleagues noted hyper-reactivity to auditory and visceral stimuli in IBS
patients.
6
Gender differences in brain activation in IBS were noted,
7
as
Defining Irritable Bowel Syndrome were differences between IBS subtypes.
8
Other studies identified several
The definition of IBS has evolved significantly over the past several regions, including the insula, anterior cingulate and somatosensory
decades. The first set of symptom-based criteria was proposed in 1978 cortices, thalamus, and limbic regions, which displayed unusual activation
by Manning and colleagues, who identified four symptoms that occurred patterns in IBS patients. Study results were often in conflict, which is not
more frequently in IBS.
3
These symptoms included looser stools at the surprising given the complicated pathophysiology that underlies IBS and
onset of pain, increased frequency of bowel movements after the onset the different methodologies employed. However, taken together, brain
of pain, relief of abdominal pain after a bowel movement, and imaging studies have consistently demonstrated significant differences in
abdominal distension. The Manning criteria had a sensitivity and activation patterns of IBS patients compared with controls. Future
specificity of 42–90% and 70–100%, respectively, but concerns soon hypothesis-driven (rather than descriptive) studies and the concurrent use
arose about their validity. The 1984 Kruis criteria placed more emphasis of imaging techniques may provide more information about the
on symptom duration; however, these criteria were quite cumbersome to pathophysiology of IBS. Additionally, new developments in imaging, such
use in clinical practice and rapidly fell out of favor. In 1988 a group of as PET tracers that allow assessment of 5-hydroxytryptamine (5-HT)
experts met in Rome to discuss functional gastrointestinal disorders serotonin synthesis within the brain, will enable researchers to track the
(FGIDs). This culminated in the publication of the Rome criteria in 1992. effects of IBS treatments.
The criteria for IBS were used in research studies but proved unwieldy in
clinical practice. In 2000 the Rome criteria were revised to the Rome II Serotonergic Agents
criteria, which also proved somewhat cumbersome in clinical practice. Multiple serotonergic agents have been used to treat IBS. Selective
serotonin re-uptake inhibitors (SSRIs) may improve visceral
The 2006 Rome III criteria contain several important changes, including a hypersensitivity, particularly in constipation-predominant IBS.
9,10
more concise and inclusive symptomatic time-frame for all FGIDs.
4
One of Furthermore, SSRIs have been shown to improve patients’ sense of
the most significant revisions concerns the classification of IBS subtypes. wellbeing, even when not depressed.
11
Tegaserod, a 5-HT4 receptor-
Subtypes are now based on stool consistency rather than stool frequency, selective agonist, is the only agent within the class of medications
and include IBS-C (constipation), IBS-D (diarrhea), IBS-M (mixed), and IBS- approved for IBS-C. Four randomized controlled trials demonstrated
U (unsubtyped). Validation studies have yet to be published, but the statistically significant improvement in global IBS symptoms.
12
Diarrhea
clinical utility of the Rome III criteria is promising. was the most common side effect, but rarely required withdrawal of the
medication.
13
Concerns over possible cardiovascular adverse events
Brain Imaging resulted in the withdrawal of tegaserod from the general market in
Functional brain imaging evaluates central nervous system activity in patients March 2007.
with IBS. The most common techniques employed in IBS brain imaging are
positron emission tomography (PET), functional magnetic resonance imaging For diarrhea-predominant IBS, alosetron, a 5-HT3 receptor antagonist,
(fMRI), and magnetoencephalography (MEG). PET uses radiolabeled isotopes has been shown to improve control of urgency over placebo in women.
14
to capture changes in neuronal metabolism or cerebral blood flow, fMRI Alosetron was taken off the market after reports of ischemic colitis and
assesses changes in the concentration of oxygenated hemoglobin, and MEG serious complications of constipation were observed. Since its removal
enables more detailed temporal resolution by mapping the magnetic fields from the market, patients with IBS have been shown to have a two- to
generated by brain activity. As these techniques measure different four-fold increased risk of ischemic colitis.
15
A recent review of clinical
parameters, they may yield divergent results. trial report forms and the US Food and Drug Administration (FDA)
70 © TOUCH BRIEFINGS 2008
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75