Amy Rothman Schonfeld

ATLANTA — Aspirin, even at low doses, appears to prevent age-related declines in gray and white matter integrity in brain regions that typically show the earliest neuropathological changes associated with Alzheimer's disease, according to Lee Ryan, Ph.D., of the departments of psychology and neuroscience of the University of Arizona at Tucson, who presented her findings at the annual meeting of the Society for Neuroscience.

These results, generated with diffusion-weighted MRI, provide visual evidence that aspirin has a neuroprotective effect on the normal brain. It supports previous epidemiologic evidence that long-term use of NSAIDs, including aspirin, decreases the risk of developing Alzheimer's disease.

Study participants included 23 cognitively healthy older (over 60 years) adults who were taking aspirin as a health precaution against vascular accidents, hypertension, or mild arthritic symptoms. Most of this group took the equivalent of one baby aspirin a day (81 mg) for up to 15 years. The control group consisted of 25 age-matched subjects not taking any NSAIDs.

Diffusion-weighted (DW) MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method. DW-MRI is thought to be “exquisitely” sensitive to the presence of inflammation and other neuropathologic processes in white and gray matter, Dr. Ryan said. Four regions of interest were analyzed: the medial temporal lobe and adjacent hippocampal white matter and the posterior cingulate and adjacent white matter in the splenium.

With DW-MRI, lower apparent diffusion coefficient (ADC) values in gray matter and higher fractional anisotropy (FA) values in white matter, compared with controls, are thought to reflect preservation of brain integrity.

Dr. Ryan found that aspirin users had significantly lower hippocampal mean ADC values and higher mean FA values in the adjacent white matter region than did controls. About 25% of both groups were positive for apolipoprotein E (ApoE), and similar protective effects from aspirin were found in individuals regardless of their ApoE status.

ADC values were not significantly different between groups in the posterior cingulate. Aspirin did, however, appear to prevent age-related functional changes in the posterior cingulate and splenium that were seen in those who did not take aspirin.

“We can't say anything about the mechanism of why diffusion is changing, but our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function,” Dr. Ryan said. “Diffusion MRI may be a sensitive measure for assessing the influence of anti-inflammatory drugs and interventions that might decrease the risk of Alzheimer's disease.”

Colored boxes represent areas assessed using DW-MRI to determine preservation of brain integrity in one subject. Courtesy Dr. Lee Ryan

'Our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function.' DR. RYAN

ATLANTA — Aspirin, even at low doses, appears to prevent age-related declines in gray and white matter integrity in brain regions that typically show the earliest neuropathological changes associated with Alzheimer's disease, according to Lee Ryan, Ph.D., of the departments of psychology and neuroscience of the University of Arizona at Tucson, who presented her findings at the annual meeting of the Society for Neuroscience.

These results, generated with diffusion-weighted MRI, provide visual evidence that aspirin has a neuroprotective effect on the normal brain. It supports previous epidemiologic evidence that long-term use of NSAIDs, including aspirin, decreases the risk of developing Alzheimer's disease.

Study participants included 23 cognitively healthy older (over 60 years) adults who were taking aspirin as a health precaution against vascular accidents, hypertension, or mild arthritic symptoms. Most of this group took the equivalent of one baby aspirin a day (81 mg) for up to 15 years. The control group consisted of 25 age-matched subjects not taking any NSAIDs.

Diffusion-weighted (DW) MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method. DW-MRI is thought to be “exquisitely” sensitive to the presence of inflammation and other neuropathologic processes in white and gray matter, Dr. Ryan said. Four regions of interest were analyzed: the medial temporal lobe and adjacent hippocampal white matter and the posterior cingulate and adjacent white matter in the splenium.

With DW-MRI, lower apparent diffusion coefficient (ADC) values in gray matter and higher fractional anisotropy (FA) values in white matter, compared with controls, are thought to reflect preservation of brain integrity.

Dr. Ryan found that aspirin users had significantly lower hippocampal mean ADC values and higher mean FA values in the adjacent white matter region than did controls. About 25% of both groups were positive for apolipoprotein E (ApoE), and similar protective effects from aspirin were found in individuals regardless of their ApoE status.

ADC values were not significantly different between groups in the posterior cingulate. Aspirin did, however, appear to prevent age-related functional changes in the posterior cingulate and splenium that were seen in those who did not take aspirin.

“We can't say anything about the mechanism of why diffusion is changing, but our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function,” Dr. Ryan said. “Diffusion MRI may be a sensitive measure for assessing the influence of anti-inflammatory drugs and interventions that might decrease the risk of Alzheimer's disease.”

Colored boxes represent areas assessed using DW-MRI to determine preservation of brain integrity in one subject. Courtesy Dr. Lee Ryan

'Our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function.' DR. RYAN

ATLANTA — Aspirin, even at low doses, appears to prevent age-related declines in gray and white matter integrity in brain regions that typically show the earliest neuropathological changes associated with Alzheimer's disease, according to Lee Ryan, Ph.D., of the departments of psychology and neuroscience of the University of Arizona at Tucson, who presented her findings at the annual meeting of the Society for Neuroscience.

These results, generated with diffusion-weighted MRI, provide visual evidence that aspirin has a neuroprotective effect on the normal brain. It supports previous epidemiologic evidence that long-term use of NSAIDs, including aspirin, decreases the risk of developing Alzheimer's disease.

Study participants included 23 cognitively healthy older (over 60 years) adults who were taking aspirin as a health precaution against vascular accidents, hypertension, or mild arthritic symptoms. Most of this group took the equivalent of one baby aspirin a day (81 mg) for up to 15 years. The control group consisted of 25 age-matched subjects not taking any NSAIDs.

Diffusion-weighted (DW) MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method. DW-MRI is thought to be “exquisitely” sensitive to the presence of inflammation and other neuropathologic processes in white and gray matter, Dr. Ryan said. Four regions of interest were analyzed: the medial temporal lobe and adjacent hippocampal white matter and the posterior cingulate and adjacent white matter in the splenium.

With DW-MRI, lower apparent diffusion coefficient (ADC) values in gray matter and higher fractional anisotropy (FA) values in white matter, compared with controls, are thought to reflect preservation of brain integrity.

Dr. Ryan found that aspirin users had significantly lower hippocampal mean ADC values and higher mean FA values in the adjacent white matter region than did controls. About 25% of both groups were positive for apolipoprotein E (ApoE), and similar protective effects from aspirin were found in individuals regardless of their ApoE status.

ADC values were not significantly different between groups in the posterior cingulate. Aspirin did, however, appear to prevent age-related functional changes in the posterior cingulate and splenium that were seen in those who did not take aspirin.

“We can't say anything about the mechanism of why diffusion is changing, but our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function,” Dr. Ryan said. “Diffusion MRI may be a sensitive measure for assessing the influence of anti-inflammatory drugs and interventions that might decrease the risk of Alzheimer's disease.”

Colored boxes represent areas assessed using DW-MRI to determine preservation of brain integrity in one subject. Courtesy Dr. Lee Ryan

'Our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function.' DR. RYAN

ATLANTA – Children who stutter have been found to have deficiencies in white-matter organization in a tract that interconnects the frontal speech/motor planning region and the posterior speech comprehension region, suggesting that inefficient connectivity among speech-relevant regions of the left hemisphere may be a possible neuroanatomical basis for stuttering, Soo-Eun Chang, Ph.D., reported in a poster at the annual meeting of the Society for Neuroscience.

Adults who stutter show the same tract abnormalities as do children, but also show asymmetry in gray-matter volume, suggesting that the gray-matter findings in adults reflect neuroplastic changes secondary to a lifetime of stuttering.

This shows “that the adult studies are compromised because there are two things going on: the original deficit, and then the neuroplasticity that is laid on top of that. This gives us a clear picture of” the actual deficit, Christy L. Ludlow, Ph.D., section chief of the National Institute of Neurological Disorders and Stroke and a coauthor of the study, said in an interview.

In their study, 22 monolingual, right-handed boys aged 9–12 years underwent high-resolution, diffusion-weighted imaging MRI studies. The group was categorized into three subgroups: normal fluent controls (seven), children who showed persistent stuttering (eight), and children who previously stuttered but had recovered and had been fluent for at least 2 years prior to scanning (seven).

When compared with normal controls, children who stutter had reduced white-matter integrity only in the left arcuate fasciculus (a tract that underlies the oral-facial motor regions).

Studies by other investigators have shown that stuttering adults manifest increased gray-matter volume in the right hemisphere, whereas fluent adults show greater left hemisphere volume. No such gray-matter asymmetry could be found in children. “In fact, they show less volume in both sides of the brain in speech areas,” which suggests that the initial deficit is different from what people see in adults, Dr. Ludlow said.

Interestingly, the left rolandic operculum abnormality was not related to ongoing stuttering, because no difference was found in this region between children who recovered and children who continued to stutter. This may indicate that the abnormality indicates a risk for stuttering, not whether there is a chance of recovery, the investigators noted.

“This is a novel finding because there haven't been any studies to date looking at the brains of children who stutter. … Our research suggests that some of the brain-imaging differences found in stuttering adults may be the result of a lifetime of coping with stuttering,” Dr. Chang said.

Children 'show less volume in both sides of the brain in speech areas.' DR. LUDLOW

MRI demonstrates significantly less white-matter integrity in the rolandic operculum in children with stuttering (both persistent and recovered). Courtesy Dr. Soo-Eun Chang

ATLANTA – Children who stutter have been found to have deficiencies in white-matter organization in a tract that interconnects the frontal speech/motor planning region and the posterior speech comprehension region, suggesting that inefficient connectivity among speech-relevant regions of the left hemisphere may be a possible neuroanatomical basis for stuttering, Soo-Eun Chang, Ph.D., reported in a poster at the annual meeting of the Society for Neuroscience.

Adults who stutter show the same tract abnormalities as do children, but also show asymmetry in gray-matter volume, suggesting that the gray-matter findings in adults reflect neuroplastic changes secondary to a lifetime of stuttering.

This shows “that the adult studies are compromised because there are two things going on: the original deficit, and then the neuroplasticity that is laid on top of that. This gives us a clear picture of” the actual deficit, Christy L. Ludlow, Ph.D., section chief of the National Institute of Neurological Disorders and Stroke and a coauthor of the study, said in an interview.

In their study, 22 monolingual, right-handed boys aged 9–12 years underwent high-resolution, diffusion-weighted imaging MRI studies. The group was categorized into three subgroups: normal fluent controls (seven), children who showed persistent stuttering (eight), and children who previously stuttered but had recovered and had been fluent for at least 2 years prior to scanning (seven).

When compared with normal controls, children who stutter had reduced white-matter integrity only in the left arcuate fasciculus (a tract that underlies the oral-facial motor regions).

Studies by other investigators have shown that stuttering adults manifest increased gray-matter volume in the right hemisphere, whereas fluent adults show greater left hemisphere volume. No such gray-matter asymmetry could be found in children. “In fact, they show less volume in both sides of the brain in speech areas,” which suggests that the initial deficit is different from what people see in adults, Dr. Ludlow said.

Interestingly, the left rolandic operculum abnormality was not related to ongoing stuttering, because no difference was found in this region between children who recovered and children who continued to stutter. This may indicate that the abnormality indicates a risk for stuttering, not whether there is a chance of recovery, the investigators noted.

“This is a novel finding because there haven't been any studies to date looking at the brains of children who stutter. … Our research suggests that some of the brain-imaging differences found in stuttering adults may be the result of a lifetime of coping with stuttering,” Dr. Chang said.

Children 'show less volume in both sides of the brain in speech areas.' DR. LUDLOW

MRI demonstrates significantly less white-matter integrity in the rolandic operculum in children with stuttering (both persistent and recovered). Courtesy Dr. Soo-Eun Chang

ATLANTA – Children who stutter have been found to have deficiencies in white-matter organization in a tract that interconnects the frontal speech/motor planning region and the posterior speech comprehension region, suggesting that inefficient connectivity among speech-relevant regions of the left hemisphere may be a possible neuroanatomical basis for stuttering, Soo-Eun Chang, Ph.D., reported in a poster at the annual meeting of the Society for Neuroscience.

Adults who stutter show the same tract abnormalities as do children, but also show asymmetry in gray-matter volume, suggesting that the gray-matter findings in adults reflect neuroplastic changes secondary to a lifetime of stuttering.

This shows “that the adult studies are compromised because there are two things going on: the original deficit, and then the neuroplasticity that is laid on top of that. This gives us a clear picture of” the actual deficit, Christy L. Ludlow, Ph.D., section chief of the National Institute of Neurological Disorders and Stroke and a coauthor of the study, said in an interview.

In their study, 22 monolingual, right-handed boys aged 9–12 years underwent high-resolution, diffusion-weighted imaging MRI studies. The group was categorized into three subgroups: normal fluent controls (seven), children who showed persistent stuttering (eight), and children who previously stuttered but had recovered and had been fluent for at least 2 years prior to scanning (seven).

When compared with normal controls, children who stutter had reduced white-matter integrity only in the left arcuate fasciculus (a tract that underlies the oral-facial motor regions).

Studies by other investigators have shown that stuttering adults manifest increased gray-matter volume in the right hemisphere, whereas fluent adults show greater left hemisphere volume. No such gray-matter asymmetry could be found in children. “In fact, they show less volume in both sides of the brain in speech areas,” which suggests that the initial deficit is different from what people see in adults, Dr. Ludlow said.

Interestingly, the left rolandic operculum abnormality was not related to ongoing stuttering, because no difference was found in this region between children who recovered and children who continued to stutter. This may indicate that the abnormality indicates a risk for stuttering, not whether there is a chance of recovery, the investigators noted.

“This is a novel finding because there haven't been any studies to date looking at the brains of children who stutter. … Our research suggests that some of the brain-imaging differences found in stuttering adults may be the result of a lifetime of coping with stuttering,” Dr. Chang said.

Children 'show less volume in both sides of the brain in speech areas.' DR. LUDLOW

MRI demonstrates significantly less white-matter integrity in the rolandic operculum in children with stuttering (both persistent and recovered). Courtesy Dr. Soo-Eun Chang

ATLANTA – Aspirin, even at low doses, appears to prevent age-related declines in gray and white matter integrity in brain regions that typically show the earliest neuropathological changes associated with Alzheimer's disease, according to Lee Ryan, Ph.D., who is with the departments of psychology and neuroscience of the University of Arizona at Tucson.

Dr. Ryan presented her findings on the impact of aspiring on brain function at the annual meeting of the Society for Neuroscience.

These results, which were generated with the use of diffusion-weighted MRI, provide visual evidence that aspirin has a neuroprotective effect on the normal brain.

In addition, the results support previous epidemiologic evidence showing that long-term use of NSAIDs, including aspirin, decreases the risk of developing Alzheimer's disease (AD).

Study participants included 23 cognitively healthy older (over 60 years) adults who were taking aspirin as a health precaution against vascular accidents, hypertension, or mild arthritic symptoms.

Most of the people in this group took the equivalent of one baby aspirin a day (81 mg) for up to 15 years. The control group consisted of 25 age-matched subjects not taking any NSAIDs.

Diffusion-weighted (DW) MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method.

DW-MRI is thought to be “exquisitely” sensitive to the presence of inflammation and other neuropathologic processes in white and gray matter, Dr. Ryan said.

The investigator analyzed four brain regions of interest: the medial temporal lobe and adjacent hippocampal white matter and the posterior cingulate and adjacent white matter in the splenium.

With DW-MRI, lower apparent diffusion coefficient (ADC) values in gray matter and higher fractional anisotropy (FA) values in white matter, compared with controls, are thought to reflect preservation of brain integrity.

Dr. Ryan found that aspirin users had significantly lower hippocampal mean ADC values and higher mean FA values in the adjacent white matter region than did controls.

According to Dr. Ryan, about 25% of both groups were positive for apolipoprotein E (ApoE), and similar protective effects from aspirin were found in individuals regardless of their ApoE status. ADC values were not significantly different between groups in the posterior cingulate.

However, the use of aspirin did appear to prevent age-related functional changes in the posterior cingulate and splenium that were seen in those who did not take aspirin.

“We can't say anything about the mechanism of why diffusion is changing, but our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function,” Dr. Ryan said.

“Diffusion MRI may be a sensitive measure for assessing the influence of anti-inflammatory drugs and interventions that might decrease the risk of Alzheimer's disease,” Dr. Ryan said.

Most of the people in the study group took the equivalent of one baby aspirin a day for up to 15 years. DR. RYAN

Colored boxes represent areas assessed using diffusion-weighted MRI scans to determine the preservation of brain integrity in one subject. The DW-MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method. Courtesy Dr. Lee Ryan

ATLANTA – Aspirin, even at low doses, appears to prevent age-related declines in gray and white matter integrity in brain regions that typically show the earliest neuropathological changes associated with Alzheimer's disease, according to Lee Ryan, Ph.D., who is with the departments of psychology and neuroscience of the University of Arizona at Tucson.

Dr. Ryan presented her findings on the impact of aspiring on brain function at the annual meeting of the Society for Neuroscience.

These results, which were generated with the use of diffusion-weighted MRI, provide visual evidence that aspirin has a neuroprotective effect on the normal brain.

In addition, the results support previous epidemiologic evidence showing that long-term use of NSAIDs, including aspirin, decreases the risk of developing Alzheimer's disease (AD).

Study participants included 23 cognitively healthy older (over 60 years) adults who were taking aspirin as a health precaution against vascular accidents, hypertension, or mild arthritic symptoms.

Most of the people in this group took the equivalent of one baby aspirin a day (81 mg) for up to 15 years. The control group consisted of 25 age-matched subjects not taking any NSAIDs.

Diffusion-weighted (DW) MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method.

DW-MRI is thought to be “exquisitely” sensitive to the presence of inflammation and other neuropathologic processes in white and gray matter, Dr. Ryan said.

The investigator analyzed four brain regions of interest: the medial temporal lobe and adjacent hippocampal white matter and the posterior cingulate and adjacent white matter in the splenium.

With DW-MRI, lower apparent diffusion coefficient (ADC) values in gray matter and higher fractional anisotropy (FA) values in white matter, compared with controls, are thought to reflect preservation of brain integrity.

Dr. Ryan found that aspirin users had significantly lower hippocampal mean ADC values and higher mean FA values in the adjacent white matter region than did controls.

According to Dr. Ryan, about 25% of both groups were positive for apolipoprotein E (ApoE), and similar protective effects from aspirin were found in individuals regardless of their ApoE status. ADC values were not significantly different between groups in the posterior cingulate.

However, the use of aspirin did appear to prevent age-related functional changes in the posterior cingulate and splenium that were seen in those who did not take aspirin.

“We can't say anything about the mechanism of why diffusion is changing, but our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function,” Dr. Ryan said.

“Diffusion MRI may be a sensitive measure for assessing the influence of anti-inflammatory drugs and interventions that might decrease the risk of Alzheimer's disease,” Dr. Ryan said.

Most of the people in the study group took the equivalent of one baby aspirin a day for up to 15 years. DR. RYAN

Colored boxes represent areas assessed using diffusion-weighted MRI scans to determine the preservation of brain integrity in one subject. The DW-MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method. Courtesy Dr. Lee Ryan

ATLANTA – Aspirin, even at low doses, appears to prevent age-related declines in gray and white matter integrity in brain regions that typically show the earliest neuropathological changes associated with Alzheimer's disease, according to Lee Ryan, Ph.D., who is with the departments of psychology and neuroscience of the University of Arizona at Tucson.

Dr. Ryan presented her findings on the impact of aspiring on brain function at the annual meeting of the Society for Neuroscience.

These results, which were generated with the use of diffusion-weighted MRI, provide visual evidence that aspirin has a neuroprotective effect on the normal brain.

In addition, the results support previous epidemiologic evidence showing that long-term use of NSAIDs, including aspirin, decreases the risk of developing Alzheimer's disease (AD).

Study participants included 23 cognitively healthy older (over 60 years) adults who were taking aspirin as a health precaution against vascular accidents, hypertension, or mild arthritic symptoms.

Most of the people in this group took the equivalent of one baby aspirin a day (81 mg) for up to 15 years. The control group consisted of 25 age-matched subjects not taking any NSAIDs.

Diffusion-weighted (DW) MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method.

DW-MRI is thought to be “exquisitely” sensitive to the presence of inflammation and other neuropathologic processes in white and gray matter, Dr. Ryan said.

The investigator analyzed four brain regions of interest: the medial temporal lobe and adjacent hippocampal white matter and the posterior cingulate and adjacent white matter in the splenium.

With DW-MRI, lower apparent diffusion coefficient (ADC) values in gray matter and higher fractional anisotropy (FA) values in white matter, compared with controls, are thought to reflect preservation of brain integrity.

Dr. Ryan found that aspirin users had significantly lower hippocampal mean ADC values and higher mean FA values in the adjacent white matter region than did controls.

According to Dr. Ryan, about 25% of both groups were positive for apolipoprotein E (ApoE), and similar protective effects from aspirin were found in individuals regardless of their ApoE status. ADC values were not significantly different between groups in the posterior cingulate.

However, the use of aspirin did appear to prevent age-related functional changes in the posterior cingulate and splenium that were seen in those who did not take aspirin.

“We can't say anything about the mechanism of why diffusion is changing, but our data support the idea that aspirin, even at low doses, may confer some positive effect on brain function,” Dr. Ryan said.

“Diffusion MRI may be a sensitive measure for assessing the influence of anti-inflammatory drugs and interventions that might decrease the risk of Alzheimer's disease,” Dr. Ryan said.

Most of the people in the study group took the equivalent of one baby aspirin a day for up to 15 years. DR. RYAN

Colored boxes represent areas assessed using diffusion-weighted MRI scans to determine the preservation of brain integrity in one subject. The DW-MRI scans were carried out on a 3-T scanner using a radial fast spin-echo method. Courtesy Dr. Lee Ryan

BOSTON — Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes—regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician-patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders—agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.

Behavioral techniques, such as cognitive-behavioral therapy, hypnosis, interpersonal psychotherapy, and stress management—often used with pharmaco- therapy—can optimize outcomes. These approaches can address many of the concerns and anxiety IBS patients have about their condition and the likelihood of improvement, and can keep patients on medications long enough for them to take effect.

BOSTON — Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes—regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician-patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders—agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.

Behavioral techniques, such as cognitive-behavioral therapy, hypnosis, interpersonal psychotherapy, and stress management—often used with pharmaco- therapy—can optimize outcomes. These approaches can address many of the concerns and anxiety IBS patients have about their condition and the likelihood of improvement, and can keep patients on medications long enough for them to take effect.

BOSTON — Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes—regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician-patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders—agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.

Behavioral techniques, such as cognitive-behavioral therapy, hypnosis, interpersonal psychotherapy, and stress management—often used with pharmaco- therapy—can optimize outcomes. These approaches can address many of the concerns and anxiety IBS patients have about their condition and the likelihood of improvement, and can keep patients on medications long enough for them to take effect.

ATLANTA — Simvastatin use for at least 7 months reduced the incidence of Alzheimer's disease by 30% and Parkinson's disease by 24% in older people, according to an analysis of a Department of Veterans Affairs pharmaceutical database.

Neither lovastatin nor atorvastatin provided similar benefits.

The protective effects of simvastatin were more prominent in people who do not have hypertension. In this subgroup, the incidence of Alzheimer's disease was reduced by 76% and the incidence of Parkinson's disease was reduced by 65%, the study's lead investigator Dr. Benjamin Wolozin reported at the annual meeting of the Society for Neuroscience.

Dr. Wolozin, a professor of pharmacology at Boston University, analyzed data from a large VA pharmaceutical database that included 4.5 million patients and more than 110 million annual medication prescriptions. Individuals were excluded if they were less than 65 years of age or had a pre-existing diagnosis of senile dementia of the Alzheimer's type.

The incidence of Alzheimer's disease among patients taking statins was compared with the incidence among patients who were not taking statins. After adjusting for age, cardiovascular disease, hypertension, and diabetes, only simvastatin use significantly lowered the incidence of Alzheimer's disease (hazard ratio 0.694).

Two different mechanisms might explain the unique effects of simvastatin compared with those of the other two statins analyzed, Dr. Wolozin said. For atorvastatin, the inability to cross the blood-brain barrier may explain its ineffectiveness. Lovastatin and simvastatin both reduce inflammation, he explained. Only simvastatin, however, inhibits cholesterol strongly enough to reduce inflammation sufficiently to protect against Alzheimer's or Parkinson's disease. Studies have shown that a biosynthetic precursor of cholesterol is required to signal inflammation. Why simvastatin is unable to reduce inflammation associated with hypertension is unclear.

Dr. Wolozin is currently analyzing the effects of several medications used chronically by older patients to investigate their impact on the incidence and progression of Alzheimer's disease. “In addition to finding medications that are therapeutically beneficial, these analyses may also tell us what kinds of factors precipitate AD in elderly people.”

Only simvastatin inhibits cholesterol enough to reduce inflammation to protect against AD and Parkinson's. DR. WOLOZIN

ELSEVIER GLOBAL MEDICAL NEWS

ATLANTA — Simvastatin use for at least 7 months reduced the incidence of Alzheimer's disease by 30% and Parkinson's disease by 24% in older people, according to an analysis of a Department of Veterans Affairs pharmaceutical database.

Neither lovastatin nor atorvastatin provided similar benefits.

The protective effects of simvastatin were more prominent in people who do not have hypertension. In this subgroup, the incidence of Alzheimer's disease was reduced by 76% and the incidence of Parkinson's disease was reduced by 65%, the study's lead investigator Dr. Benjamin Wolozin reported at the annual meeting of the Society for Neuroscience.

Dr. Wolozin, a professor of pharmacology at Boston University, analyzed data from a large VA pharmaceutical database that included 4.5 million patients and more than 110 million annual medication prescriptions. Individuals were excluded if they were less than 65 years of age or had a pre-existing diagnosis of senile dementia of the Alzheimer's type.

The incidence of Alzheimer's disease among patients taking statins was compared with the incidence among patients who were not taking statins. After adjusting for age, cardiovascular disease, hypertension, and diabetes, only simvastatin use significantly lowered the incidence of Alzheimer's disease (hazard ratio 0.694).

Two different mechanisms might explain the unique effects of simvastatin compared with those of the other two statins analyzed, Dr. Wolozin said. For atorvastatin, the inability to cross the blood-brain barrier may explain its ineffectiveness. Lovastatin and simvastatin both reduce inflammation, he explained. Only simvastatin, however, inhibits cholesterol strongly enough to reduce inflammation sufficiently to protect against Alzheimer's or Parkinson's disease. Studies have shown that a biosynthetic precursor of cholesterol is required to signal inflammation. Why simvastatin is unable to reduce inflammation associated with hypertension is unclear.

Dr. Wolozin is currently analyzing the effects of several medications used chronically by older patients to investigate their impact on the incidence and progression of Alzheimer's disease. “In addition to finding medications that are therapeutically beneficial, these analyses may also tell us what kinds of factors precipitate AD in elderly people.”

Only simvastatin inhibits cholesterol enough to reduce inflammation to protect against AD and Parkinson's. DR. WOLOZIN

ELSEVIER GLOBAL MEDICAL NEWS

ATLANTA — Simvastatin use for at least 7 months reduced the incidence of Alzheimer's disease by 30% and Parkinson's disease by 24% in older people, according to an analysis of a Department of Veterans Affairs pharmaceutical database.

Neither lovastatin nor atorvastatin provided similar benefits.

The protective effects of simvastatin were more prominent in people who do not have hypertension. In this subgroup, the incidence of Alzheimer's disease was reduced by 76% and the incidence of Parkinson's disease was reduced by 65%, the study's lead investigator Dr. Benjamin Wolozin reported at the annual meeting of the Society for Neuroscience.

Dr. Wolozin, a professor of pharmacology at Boston University, analyzed data from a large VA pharmaceutical database that included 4.5 million patients and more than 110 million annual medication prescriptions. Individuals were excluded if they were less than 65 years of age or had a pre-existing diagnosis of senile dementia of the Alzheimer's type.

The incidence of Alzheimer's disease among patients taking statins was compared with the incidence among patients who were not taking statins. After adjusting for age, cardiovascular disease, hypertension, and diabetes, only simvastatin use significantly lowered the incidence of Alzheimer's disease (hazard ratio 0.694).

Two different mechanisms might explain the unique effects of simvastatin compared with those of the other two statins analyzed, Dr. Wolozin said. For atorvastatin, the inability to cross the blood-brain barrier may explain its ineffectiveness. Lovastatin and simvastatin both reduce inflammation, he explained. Only simvastatin, however, inhibits cholesterol strongly enough to reduce inflammation sufficiently to protect against Alzheimer's or Parkinson's disease. Studies have shown that a biosynthetic precursor of cholesterol is required to signal inflammation. Why simvastatin is unable to reduce inflammation associated with hypertension is unclear.

Dr. Wolozin is currently analyzing the effects of several medications used chronically by older patients to investigate their impact on the incidence and progression of Alzheimer's disease. “In addition to finding medications that are therapeutically beneficial, these analyses may also tell us what kinds of factors precipitate AD in elderly people.”

Only simvastatin inhibits cholesterol enough to reduce inflammation to protect against AD and Parkinson's. DR. WOLOZIN

ELSEVIER GLOBAL MEDICAL NEWS

A clinical expert consensus document has been issued by the American College of Cardiology Foundation to inform and guide clinical practice regarding the use of carotid stenting.

“This is the first multidisciplinary document of its type on carotid artery stenting,” Dr. Eric R. Bates, chair of the writing committee, said in an interview. Dr. Bates explained that while there is not enough rigorous evidence available to allow the formulation of evidence-based guidelines, the suggestions made in the consensus document represent a state-of-the-art summary derived from the experience of well-credentialed investigators and the results of registries and clinical trials.

The document is cosponsored by the Society for Cardiovascular Angiography and Interventions, the Society for Vascular Medicine and Biology, the Society for Interventional Radiology, and the American Society of Interventional and Therapeutic Neuroradiology (J. Am. Coll. Cardiol. 2007;49:126–70).

Representatives of six professional societies, including cardiologists, interventional radiologists, neurointerventionalists, and a neurologist, composed the 15-member writing committee. One surgeon was included, but the document was not endorsed by a surgical organization.

Of the almost 1 million stroke-related events occurring in the United States each year, about 5%–12% are caused by carotid occlusive disease that is amenable to revascularization. The consensus document endorses current American Heart Association guidelines that recommend carotid endarterectomy (CEA) in symptomatic patients with stenosis 50%–99%, if the risk of perioperative stroke or death is less than 6%. For asymptomatic patients, CEA is recommended for stenosis 60%–99%, if the risk of perioperative stroke or death is less than 3%, although stenosis greater than 80% is the commonly accepted clinical standard. American Academy of Neurology guidelines indicate that patients eligible for carotid artery stenting (CAS) should be 40–75 years old and have a life expectancy of at least 5 years.

“Although CAS is a new treatment and is still undergoing development and testing, right now it is a reasonable alternative to CEA, especially in patients who are at high risk for CEA,” said Dr. Bates, professor of internal medicine and director of cardiac catheterization at the University of Michigan, Ann Arbor.

When stenting the carotid artery, embolic protection devices (EPDs) should be used to reduce the risk of procedure-related stroke, despite the current lack of randomized studies comparing CAS with and without EPDs, the committee recommends. Physicians who perform CAS must also be skilled in placing EPDs.

Current Centers for Medicare and Medicaid Services reimbursement criteria for carotid stenting is limited to individuals at high risk for CEA with symptomatic stenosis greater than 70%, performed by qualified physicians at qualified institutions using Food and Drug Administration-approved stents. Stenting is reimbursed for high-risk patients (symptomatic stenosis greater than 50% or asymptomatic stenosis greater than 80%) in a Category B Investigational Device Exemption trial or postapproval study.

Due to insufficient evidence, CAS is not recommended for high-risk patients with asymptomatic stenosis of less than 80% or in any patient without high-risk features, and the consensus document suggests that further investigation is needed to evaluate the relative merits of CAS compared with optimal medical therapy. “The benefits of revascularization are negated if the risk of revascularization is high, and the fact that CEA is associated with more risk does not mandate that patients undergo CAS.” The role of CAS in low-risk patients also awaits further clarification.

The document also examined the issues of training and credentialing operators who perform CAS. Operators come from various subspecialties—mostly cardiologists, surgeons, and radiologists—with different backgrounds, experience, and expertise. Regardless of specialty, all “operators should previously have achieved a high level of proficiency in catheter-based intervention, complete dedicated training in CAS, and be credentialed at their hospital.” Operators and institutions are required to track and report outcomes to a national database.

“We tried to go for a fair and balanced document that represents all viewpoints,” said Dr. Gary R. Duckwiler, an interventional neuroradiologist at the University of California, Los Angeles, and a member of the writing committee. “There were areas of significant disagreement about the preparatory training and knowledge necessary to perform CAS, and those are identified in the document. For the most part, we all agree that carotid stenting, at least based on the data we have now, can be an excellent procedure in the appropriate patients.”

CAS, although new, 'is a reasonable alternative to CEA, especially in patients who are at high risk for CEA.' DR. BATES

A clinical expert consensus document has been issued by the American College of Cardiology Foundation to inform and guide clinical practice regarding the use of carotid stenting.

“This is the first multidisciplinary document of its type on carotid artery stenting,” Dr. Eric R. Bates, chair of the writing committee, said in an interview. Dr. Bates explained that while there is not enough rigorous evidence available to allow the formulation of evidence-based guidelines, the suggestions made in the consensus document represent a state-of-the-art summary derived from the experience of well-credentialed investigators and the results of registries and clinical trials.

The document is cosponsored by the Society for Cardiovascular Angiography and Interventions, the Society for Vascular Medicine and Biology, the Society for Interventional Radiology, and the American Society of Interventional and Therapeutic Neuroradiology (J. Am. Coll. Cardiol. 2007;49:126–70).

Representatives of six professional societies, including cardiologists, interventional radiologists, neurointerventionalists, and a neurologist, composed the 15-member writing committee. One surgeon was included, but the document was not endorsed by a surgical organization.

Of the almost 1 million stroke-related events occurring in the United States each year, about 5%–12% are caused by carotid occlusive disease that is amenable to revascularization. The consensus document endorses current American Heart Association guidelines that recommend carotid endarterectomy (CEA) in symptomatic patients with stenosis 50%–99%, if the risk of perioperative stroke or death is less than 6%. For asymptomatic patients, CEA is recommended for stenosis 60%–99%, if the risk of perioperative stroke or death is less than 3%, although stenosis greater than 80% is the commonly accepted clinical standard. American Academy of Neurology guidelines indicate that patients eligible for carotid artery stenting (CAS) should be 40–75 years old and have a life expectancy of at least 5 years.

“Although CAS is a new treatment and is still undergoing development and testing, right now it is a reasonable alternative to CEA, especially in patients who are at high risk for CEA,” said Dr. Bates, professor of internal medicine and director of cardiac catheterization at the University of Michigan, Ann Arbor.

When stenting the carotid artery, embolic protection devices (EPDs) should be used to reduce the risk of procedure-related stroke, despite the current lack of randomized studies comparing CAS with and without EPDs, the committee recommends. Physicians who perform CAS must also be skilled in placing EPDs.

Current Centers for Medicare and Medicaid Services reimbursement criteria for carotid stenting is limited to individuals at high risk for CEA with symptomatic stenosis greater than 70%, performed by qualified physicians at qualified institutions using Food and Drug Administration-approved stents. Stenting is reimbursed for high-risk patients (symptomatic stenosis greater than 50% or asymptomatic stenosis greater than 80%) in a Category B Investigational Device Exemption trial or postapproval study.

Due to insufficient evidence, CAS is not recommended for high-risk patients with asymptomatic stenosis of less than 80% or in any patient without high-risk features, and the consensus document suggests that further investigation is needed to evaluate the relative merits of CAS compared with optimal medical therapy. “The benefits of revascularization are negated if the risk of revascularization is high, and the fact that CEA is associated with more risk does not mandate that patients undergo CAS.” The role of CAS in low-risk patients also awaits further clarification.

The document also examined the issues of training and credentialing operators who perform CAS. Operators come from various subspecialties—mostly cardiologists, surgeons, and radiologists—with different backgrounds, experience, and expertise. Regardless of specialty, all “operators should previously have achieved a high level of proficiency in catheter-based intervention, complete dedicated training in CAS, and be credentialed at their hospital.” Operators and institutions are required to track and report outcomes to a national database.

“We tried to go for a fair and balanced document that represents all viewpoints,” said Dr. Gary R. Duckwiler, an interventional neuroradiologist at the University of California, Los Angeles, and a member of the writing committee. “There were areas of significant disagreement about the preparatory training and knowledge necessary to perform CAS, and those are identified in the document. For the most part, we all agree that carotid stenting, at least based on the data we have now, can be an excellent procedure in the appropriate patients.”

CAS, although new, 'is a reasonable alternative to CEA, especially in patients who are at high risk for CEA.' DR. BATES

A clinical expert consensus document has been issued by the American College of Cardiology Foundation to inform and guide clinical practice regarding the use of carotid stenting.

“This is the first multidisciplinary document of its type on carotid artery stenting,” Dr. Eric R. Bates, chair of the writing committee, said in an interview. Dr. Bates explained that while there is not enough rigorous evidence available to allow the formulation of evidence-based guidelines, the suggestions made in the consensus document represent a state-of-the-art summary derived from the experience of well-credentialed investigators and the results of registries and clinical trials.

The document is cosponsored by the Society for Cardiovascular Angiography and Interventions, the Society for Vascular Medicine and Biology, the Society for Interventional Radiology, and the American Society of Interventional and Therapeutic Neuroradiology (J. Am. Coll. Cardiol. 2007;49:126–70).

Representatives of six professional societies, including cardiologists, interventional radiologists, neurointerventionalists, and a neurologist, composed the 15-member writing committee. One surgeon was included, but the document was not endorsed by a surgical organization.

Of the almost 1 million stroke-related events occurring in the United States each year, about 5%–12% are caused by carotid occlusive disease that is amenable to revascularization. The consensus document endorses current American Heart Association guidelines that recommend carotid endarterectomy (CEA) in symptomatic patients with stenosis 50%–99%, if the risk of perioperative stroke or death is less than 6%. For asymptomatic patients, CEA is recommended for stenosis 60%–99%, if the risk of perioperative stroke or death is less than 3%, although stenosis greater than 80% is the commonly accepted clinical standard. American Academy of Neurology guidelines indicate that patients eligible for carotid artery stenting (CAS) should be 40–75 years old and have a life expectancy of at least 5 years.

“Although CAS is a new treatment and is still undergoing development and testing, right now it is a reasonable alternative to CEA, especially in patients who are at high risk for CEA,” said Dr. Bates, professor of internal medicine and director of cardiac catheterization at the University of Michigan, Ann Arbor.

When stenting the carotid artery, embolic protection devices (EPDs) should be used to reduce the risk of procedure-related stroke, despite the current lack of randomized studies comparing CAS with and without EPDs, the committee recommends. Physicians who perform CAS must also be skilled in placing EPDs.

Current Centers for Medicare and Medicaid Services reimbursement criteria for carotid stenting is limited to individuals at high risk for CEA with symptomatic stenosis greater than 70%, performed by qualified physicians at qualified institutions using Food and Drug Administration-approved stents. Stenting is reimbursed for high-risk patients (symptomatic stenosis greater than 50% or asymptomatic stenosis greater than 80%) in a Category B Investigational Device Exemption trial or postapproval study.

Due to insufficient evidence, CAS is not recommended for high-risk patients with asymptomatic stenosis of less than 80% or in any patient without high-risk features, and the consensus document suggests that further investigation is needed to evaluate the relative merits of CAS compared with optimal medical therapy. “The benefits of revascularization are negated if the risk of revascularization is high, and the fact that CEA is associated with more risk does not mandate that patients undergo CAS.” The role of CAS in low-risk patients also awaits further clarification.

The document also examined the issues of training and credentialing operators who perform CAS. Operators come from various subspecialties—mostly cardiologists, surgeons, and radiologists—with different backgrounds, experience, and expertise. Regardless of specialty, all “operators should previously have achieved a high level of proficiency in catheter-based intervention, complete dedicated training in CAS, and be credentialed at their hospital.” Operators and institutions are required to track and report outcomes to a national database.

“We tried to go for a fair and balanced document that represents all viewpoints,” said Dr. Gary R. Duckwiler, an interventional neuroradiologist at the University of California, Los Angeles, and a member of the writing committee. “There were areas of significant disagreement about the preparatory training and knowledge necessary to perform CAS, and those are identified in the document. For the most part, we all agree that carotid stenting, at least based on the data we have now, can be an excellent procedure in the appropriate patients.”

CAS, although new, 'is a reasonable alternative to CEA, especially in patients who are at high risk for CEA.' DR. BATES

BOSTON — Cyclic vomiting syndrome in adults often goes unrecognized for years after onset, despite its severe and disabling consequences.

The disorder may be the cause of repeat visits to emergency departments, unnecessary surgeries and diagnostic tests, and substance abuse, according to participants at the first-ever symposium devoted to cyclic vomiting syndrome (CVS) in adults. The gathering was held as a satellite meeting following a meeting on neurogastroenterology and motility.

Diagnosis of CVS in adults is complicated by the variability in age of onset and pattern of symptoms. The result is that the average delay in making the diagnosis is 8 years from the time symptoms first appear, noted Dr. B. U.K. Li, director of the Center for CVS at the Medical College of Wisconsin, Milwaukee, in a presentation at the meeting.

“Where were we? How did we miss these folks?” Dr. Richard McCallum of the Kansas University Medical Center, Kansas City, rhetorically asked the audience, composed of physicians, patients, and family members.

As the director of the first center for CVS in adults, Dr. McCallum said, “We're getting a continued trickle of patients coming to us, and an avalanche of phone calls from patients and physicians from around the world.”

According to the Rome 3 criteria H1b, the definition of CVS is two or more periods of intense nausea or unremitting vomiting or retching lasting hours to days, with a return to the usual state of health lasting weeks to months (J. Gastro. Liver Dis. 2006;15:237–41). In its mildest form, the symptoms of CVS do not interfere with a patient's ability to work or attend school, said Dr. David Fleisher of the University of Missouri, Columbia, who has studied 41 adults with CVS.

He found that about 8% of his sample had mild symptoms, 44% had moderate symptoms that caused them to worry about their ability to continue work or school, and about 49% had incapacitating symptoms so severe that they were sick more often than they were well.

Some of these patients experienced eight or more vomiting episodes per hour for months on end, leading in some cases to more than 100 visits to the emergency department or hospitalizations. As CVS progresses, episodes may become more frequent with less time for recovery, a process Dr. Fleisher terms “coalescence.”

When rushed to the emergency department during the emetic phase, CVS patients can present with blood in the vomitus due to prolapse gastropathy or Mallory-Weiss tears resulting from forceful heaves, erosive esophagitis, and aspiration. Dehydration and electrolyte imbalance, particularly hypokalemia, may accompany the GI symptoms.

Patients often experience intense abdominal pain, and may demand narcotics; they may show signs of narcotic dependence. Tooth decay can be evident, and patients may describe chronic weight loss, Dr. Fleisher said.

Patients also may show signs of a hyperadrenergic state, including low-grade fever, rapid pulse, and hypertension. Neutrophilia without bandemia, accompanied by abdominal pain and vomiting, may be mis- diagnosed as pancreatitis, peptic ulcer, appendicitis, or pyelonephritis. The periodicity of attacks, with or without hypertension, may lead to confusion and give the impression of porphyria, pheochromocytoma, abdominal epilepsy, intermittent small bowel obstruction, or endometriosis.

Patients also may present with unusual behaviors and mental states that compound the difficulty of identifying CVS. Normally pleasant and affable patients may become irritable and verbally abusive, demanding medications. Patients may describe thirst so intense that they drink surreptitiously from toilet bowls. They may engage in a guzzle-and-vomit sequence that can be mistaken for bulimia, and which may actually be explained by the transient relief provided by sudden emptying of the stomach.

Other patients may ask for repeated hot showers or baths. Some patients may appear so immobile that it is difficult to establish whether they are asleep or awake; they also may withdraw from social contact, a frightening condition Dr. Fleisher describes as “conscious coma.”

CVS patients often undergo batteries of tests, including upper GI series, abdominal ultrasound and CT scan, colonoscopy, barium enema, endoscopy, MRI of the head, sinus radiography, EEG, and lab work, usually with negative results.

In Dr. Fleisher's series, the 41 patients underwent almost 300 diagnostic studies—none of which were indicative of an organic etiology for CVS. Recent findings suggest that about 75% of patients with CVS show rapid gastric emptying on electrogastrograms, and this may help distinguish CVS from other vomiting disorders (Neurogastroenterol. Motil. 2006;18:728 [abstract 200]).

Unnecessary surgeries are also common. Of the 41 patients in the series, 10 had undergone cholecystectomies, 2 had appendectomies, 5 had laparoscopies, 1 had a hysterectomy, and others had undergone other GI procedures. None of these procedures relieved the CVS symptoms.

Part of the problem is the lack of continuity of care for these patients, especially those who present repeatedly to hospital emergency departments. Dr. Fleisher suggests that more CVS centers should be created and staffed by two to three physicians available 24/7, as well as by nurses and mental health professionals. A patient can be managed routinely by his primary care physician, and then referred when necessary to a CVS center cognizant of his history, he added.

The Cyclic Vomiting Syndrome Association (www.cvsaonline.org

The average delay in making the diagnosis of CVS is 8 years from the time symptoms first appear. DR. LI

Knowledge, Patience Key to Managing the Four Phases of Cyclic Vomiting Syndrome

A physician must be knowledgeable, accessible, patient, nonjudgmental, and quick to respond when treating adults with cyclic vomiting syndrome, Dr. Fleisher said, and follow a rational treatment plan, tailored to the phase of the disease, that includes sedation when symptoms rage uncontrollably.

The CVS cycle has four phases, said Dr. Fleisher, who has treated more than 350 pediatric and adult CVS patients at the University of Missouri Hospital and Clinics, Columbia. The time between episodes, when the patient is feeling well, can be considered the first phase. The goal in this phase is to prevent a CVS episode by recognizing and controlling triggers, such as menstruation, noxious stress, pleasant excitement, fatigue, or infection. Some patients have interepisodic dyspeptic nausea and abdominal discomfort, especially in the mornings, and they may respond to proton-pump inhibitors.

The physician should help the patient regain a sense of being in control, rather than being at the mercy of CVS symptoms; this can be critical in determining overall treatment success, he said.

Dr. Fleisher considers CVS to be a manifestation of migraine diathesis in some patients. In a group of 41 adults with CVS, 70% had migraines during or between episodes, and 57% had first- and/or second-degree relatives with migraines. For these patients, migraine prophylaxis is essential to prevent CVS symptoms.

For two-thirds of Dr. Fleisher's group, severe anxiety and panic attacks triggered CVS episodes, and the panic symptoms persisted for hours or days. He likens the symptoms to those of an “adrenergic storm” seen in patients with pheochromocytoma. Patients begin to fall into a vicious cycle of anticipatory anxiety, whereby the worry about having a CVS episode increases the likelihood of another attack.

Some CVS patients have a propensity to both migraines and anxiety/panic attacks. A careful medical history can help physicians recognize the pathogenic factors specific for each patient, leading to an appropriate preventive strategy.

In the prodromal phase, the physician and patient have the chance to abort the emetic phase. In Dr. Fleisher's group, 93% had recognizable prodromes; common symptoms included nausea, sweating, epigastric pain or pressure, fatigue or weakness, feeling hot or cold, cramping urge to defecate, abdominal pain, shivering or shakiness, insomnia, food aversion, palpitations, irritability, and panic.

Depending on the symptom, appropriate medications during the prodrome include lorazepam, alprazolam, and/or ondansetron orally or sublingually for nausea, analgesics for abdominal pain, antianxiety medications for anxiety, and a triptan for headaches. Sleep may also be beneficial.

During the emetic phase, the goal is to rapidly terminate the episode, preferably within 1 hour of onset. In a sample of 39 adults with CVS, more than half had vomiting episodes lasting 3 days or more. Steps to take include prevention or correction of dehydration with IV fluids, and IV administration of antiemetics, antianxiolytic agents, and H2-receptor blockers or proton-pump inhibitors. In some cases, IV opiates are necessary for pain control. Patients should be checked for electrolyte depletion, tetany, hematemesis, and secretion of inappropriate antidiuretic hormone.

If the CVS episode cannot be terminated, Dr. Fleisher recommends sedating the patient in a dimly lit and quiet room until the episode passes. “A CVS patient needs to know there is an escape hatch that gets them out of their misery. Without that, the more they will suffer and the more they will coalesce,” Dr. Fleisher said, referring to the process in which CVS episodes become more and more frequent. He recommends chlorpromazine (0.5–1.0 mg/kg) plus diphenhydramine (0.5–1.0 mg/kg) in normal saline over 15 minutes, which can be repeated as often as every 3–4 hours if needed.

The duration of the recovery period reflects the adequacy of management of the emetic phase. Patients with severe fluid or electrolyte deficits will have a more difficult and prolonged recovery. Some patients can tolerate a normal diet soon after the emetic phase passes, while others will tolerate only clear liquids.

“Long waits in emergency rooms, encounters with caregivers who are unfamiliar with CVS, receiving implausible diagnoses, the repetition of unrewarding diagnostic procedures, and stopgap intravenous hydration followed by being sent home still sick are common experiences that reinforce patients' feelings of being out of control of an illness that no one understands or can treat,” Dr. Fleisher wrote in a 2005 report on the 41 patients (see

www.biomedcentral.com/1741-7015/3/20

BOSTON — Cyclic vomiting syndrome in adults often goes unrecognized for years after onset, despite its severe and disabling consequences.

The disorder may be the cause of repeat visits to emergency departments, unnecessary surgeries and diagnostic tests, and substance abuse, according to participants at the first-ever symposium devoted to cyclic vomiting syndrome (CVS) in adults. The gathering was held as a satellite meeting following a meeting on neurogastroenterology and motility.

Diagnosis of CVS in adults is complicated by the variability in age of onset and pattern of symptoms. The result is that the average delay in making the diagnosis is 8 years from the time symptoms first appear, noted Dr. B. U.K. Li, director of the Center for CVS at the Medical College of Wisconsin, Milwaukee, in a presentation at the meeting.

“Where were we? How did we miss these folks?” Dr. Richard McCallum of the Kansas University Medical Center, Kansas City, rhetorically asked the audience, composed of physicians, patients, and family members.

As the director of the first center for CVS in adults, Dr. McCallum said, “We're getting a continued trickle of patients coming to us, and an avalanche of phone calls from patients and physicians from around the world.”

According to the Rome 3 criteria H1b, the definition of CVS is two or more periods of intense nausea or unremitting vomiting or retching lasting hours to days, with a return to the usual state of health lasting weeks to months (J. Gastro. Liver Dis. 2006;15:237–41). In its mildest form, the symptoms of CVS do not interfere with a patient's ability to work or attend school, said Dr. David Fleisher of the University of Missouri, Columbia, who has studied 41 adults with CVS.

He found that about 8% of his sample had mild symptoms, 44% had moderate symptoms that caused them to worry about their ability to continue work or school, and about 49% had incapacitating symptoms so severe that they were sick more often than they were well.

Some of these patients experienced eight or more vomiting episodes per hour for months on end, leading in some cases to more than 100 visits to the emergency department or hospitalizations. As CVS progresses, episodes may become more frequent with less time for recovery, a process Dr. Fleisher terms “coalescence.”

When rushed to the emergency department during the emetic phase, CVS patients can present with blood in the vomitus due to prolapse gastropathy or Mallory-Weiss tears resulting from forceful heaves, erosive esophagitis, and aspiration. Dehydration and electrolyte imbalance, particularly hypokalemia, may accompany the GI symptoms.

Patients often experience intense abdominal pain, and may demand narcotics; they may show signs of narcotic dependence. Tooth decay can be evident, and patients may describe chronic weight loss, Dr. Fleisher said.

Patients also may show signs of a hyperadrenergic state, including low-grade fever, rapid pulse, and hypertension. Neutrophilia without bandemia, accompanied by abdominal pain and vomiting, may be mis- diagnosed as pancreatitis, peptic ulcer, appendicitis, or pyelonephritis. The periodicity of attacks, with or without hypertension, may lead to confusion and give the impression of porphyria, pheochromocytoma, abdominal epilepsy, intermittent small bowel obstruction, or endometriosis.

Patients also may present with unusual behaviors and mental states that compound the difficulty of identifying CVS. Normally pleasant and affable patients may become irritable and verbally abusive, demanding medications. Patients may describe thirst so intense that they drink surreptitiously from toilet bowls. They may engage in a guzzle-and-vomit sequence that can be mistaken for bulimia, and which may actually be explained by the transient relief provided by sudden emptying of the stomach.

Other patients may ask for repeated hot showers or baths. Some patients may appear so immobile that it is difficult to establish whether they are asleep or awake; they also may withdraw from social contact, a frightening condition Dr. Fleisher describes as “conscious coma.”

CVS patients often undergo batteries of tests, including upper GI series, abdominal ultrasound and CT scan, colonoscopy, barium enema, endoscopy, MRI of the head, sinus radiography, EEG, and lab work, usually with negative results.

In Dr. Fleisher's series, the 41 patients underwent almost 300 diagnostic studies—none of which were indicative of an organic etiology for CVS. Recent findings suggest that about 75% of patients with CVS show rapid gastric emptying on electrogastrograms, and this may help distinguish CVS from other vomiting disorders (Neurogastroenterol. Motil. 2006;18:728 [abstract 200]).

Unnecessary surgeries are also common. Of the 41 patients in the series, 10 had undergone cholecystectomies, 2 had appendectomies, 5 had laparoscopies, 1 had a hysterectomy, and others had undergone other GI procedures. None of these procedures relieved the CVS symptoms.

Part of the problem is the lack of continuity of care for these patients, especially those who present repeatedly to hospital emergency departments. Dr. Fleisher suggests that more CVS centers should be created and staffed by two to three physicians available 24/7, as well as by nurses and mental health professionals. A patient can be managed routinely by his primary care physician, and then referred when necessary to a CVS center cognizant of his history, he added.

The Cyclic Vomiting Syndrome Association (www.cvsaonline.org

The average delay in making the diagnosis of CVS is 8 years from the time symptoms first appear. DR. LI

Knowledge, Patience Key to Managing the Four Phases of Cyclic Vomiting Syndrome

A physician must be knowledgeable, accessible, patient, nonjudgmental, and quick to respond when treating adults with cyclic vomiting syndrome, Dr. Fleisher said, and follow a rational treatment plan, tailored to the phase of the disease, that includes sedation when symptoms rage uncontrollably.

The CVS cycle has four phases, said Dr. Fleisher, who has treated more than 350 pediatric and adult CVS patients at the University of Missouri Hospital and Clinics, Columbia. The time between episodes, when the patient is feeling well, can be considered the first phase. The goal in this phase is to prevent a CVS episode by recognizing and controlling triggers, such as menstruation, noxious stress, pleasant excitement, fatigue, or infection. Some patients have interepisodic dyspeptic nausea and abdominal discomfort, especially in the mornings, and they may respond to proton-pump inhibitors.

The physician should help the patient regain a sense of being in control, rather than being at the mercy of CVS symptoms; this can be critical in determining overall treatment success, he said.

Dr. Fleisher considers CVS to be a manifestation of migraine diathesis in some patients. In a group of 41 adults with CVS, 70% had migraines during or between episodes, and 57% had first- and/or second-degree relatives with migraines. For these patients, migraine prophylaxis is essential to prevent CVS symptoms.

For two-thirds of Dr. Fleisher's group, severe anxiety and panic attacks triggered CVS episodes, and the panic symptoms persisted for hours or days. He likens the symptoms to those of an “adrenergic storm” seen in patients with pheochromocytoma. Patients begin to fall into a vicious cycle of anticipatory anxiety, whereby the worry about having a CVS episode increases the likelihood of another attack.

Some CVS patients have a propensity to both migraines and anxiety/panic attacks. A careful medical history can help physicians recognize the pathogenic factors specific for each patient, leading to an appropriate preventive strategy.

In the prodromal phase, the physician and patient have the chance to abort the emetic phase. In Dr. Fleisher's group, 93% had recognizable prodromes; common symptoms included nausea, sweating, epigastric pain or pressure, fatigue or weakness, feeling hot or cold, cramping urge to defecate, abdominal pain, shivering or shakiness, insomnia, food aversion, palpitations, irritability, and panic.

Depending on the symptom, appropriate medications during the prodrome include lorazepam, alprazolam, and/or ondansetron orally or sublingually for nausea, analgesics for abdominal pain, antianxiety medications for anxiety, and a triptan for headaches. Sleep may also be beneficial.

During the emetic phase, the goal is to rapidly terminate the episode, preferably within 1 hour of onset. In a sample of 39 adults with CVS, more than half had vomiting episodes lasting 3 days or more. Steps to take include prevention or correction of dehydration with IV fluids, and IV administration of antiemetics, antianxiolytic agents, and H2-receptor blockers or proton-pump inhibitors. In some cases, IV opiates are necessary for pain control. Patients should be checked for electrolyte depletion, tetany, hematemesis, and secretion of inappropriate antidiuretic hormone.

If the CVS episode cannot be terminated, Dr. Fleisher recommends sedating the patient in a dimly lit and quiet room until the episode passes. “A CVS patient needs to know there is an escape hatch that gets them out of their misery. Without that, the more they will suffer and the more they will coalesce,” Dr. Fleisher said, referring to the process in which CVS episodes become more and more frequent. He recommends chlorpromazine (0.5–1.0 mg/kg) plus diphenhydramine (0.5–1.0 mg/kg) in normal saline over 15 minutes, which can be repeated as often as every 3–4 hours if needed.

The duration of the recovery period reflects the adequacy of management of the emetic phase. Patients with severe fluid or electrolyte deficits will have a more difficult and prolonged recovery. Some patients can tolerate a normal diet soon after the emetic phase passes, while others will tolerate only clear liquids.

“Long waits in emergency rooms, encounters with caregivers who are unfamiliar with CVS, receiving implausible diagnoses, the repetition of unrewarding diagnostic procedures, and stopgap intravenous hydration followed by being sent home still sick are common experiences that reinforce patients' feelings of being out of control of an illness that no one understands or can treat,” Dr. Fleisher wrote in a 2005 report on the 41 patients (see

www.biomedcentral.com/1741-7015/3/20

BOSTON — Cyclic vomiting syndrome in adults often goes unrecognized for years after onset, despite its severe and disabling consequences.

The disorder may be the cause of repeat visits to emergency departments, unnecessary surgeries and diagnostic tests, and substance abuse, according to participants at the first-ever symposium devoted to cyclic vomiting syndrome (CVS) in adults. The gathering was held as a satellite meeting following a meeting on neurogastroenterology and motility.

Diagnosis of CVS in adults is complicated by the variability in age of onset and pattern of symptoms. The result is that the average delay in making the diagnosis is 8 years from the time symptoms first appear, noted Dr. B. U.K. Li, director of the Center for CVS at the Medical College of Wisconsin, Milwaukee, in a presentation at the meeting.

“Where were we? How did we miss these folks?” Dr. Richard McCallum of the Kansas University Medical Center, Kansas City, rhetorically asked the audience, composed of physicians, patients, and family members.

As the director of the first center for CVS in adults, Dr. McCallum said, “We're getting a continued trickle of patients coming to us, and an avalanche of phone calls from patients and physicians from around the world.”

According to the Rome 3 criteria H1b, the definition of CVS is two or more periods of intense nausea or unremitting vomiting or retching lasting hours to days, with a return to the usual state of health lasting weeks to months (J. Gastro. Liver Dis. 2006;15:237–41). In its mildest form, the symptoms of CVS do not interfere with a patient's ability to work or attend school, said Dr. David Fleisher of the University of Missouri, Columbia, who has studied 41 adults with CVS.

He found that about 8% of his sample had mild symptoms, 44% had moderate symptoms that caused them to worry about their ability to continue work or school, and about 49% had incapacitating symptoms so severe that they were sick more often than they were well.

Some of these patients experienced eight or more vomiting episodes per hour for months on end, leading in some cases to more than 100 visits to the emergency department or hospitalizations. As CVS progresses, episodes may become more frequent with less time for recovery, a process Dr. Fleisher terms “coalescence.”

When rushed to the emergency department during the emetic phase, CVS patients can present with blood in the vomitus due to prolapse gastropathy or Mallory-Weiss tears resulting from forceful heaves, erosive esophagitis, and aspiration. Dehydration and electrolyte imbalance, particularly hypokalemia, may accompany the GI symptoms.

Patients often experience intense abdominal pain, and may demand narcotics; they may show signs of narcotic dependence. Tooth decay can be evident, and patients may describe chronic weight loss, Dr. Fleisher said.

Patients also may show signs of a hyperadrenergic state, including low-grade fever, rapid pulse, and hypertension. Neutrophilia without bandemia, accompanied by abdominal pain and vomiting, may be mis- diagnosed as pancreatitis, peptic ulcer, appendicitis, or pyelonephritis. The periodicity of attacks, with or without hypertension, may lead to confusion and give the impression of porphyria, pheochromocytoma, abdominal epilepsy, intermittent small bowel obstruction, or endometriosis.

Patients also may present with unusual behaviors and mental states that compound the difficulty of identifying CVS. Normally pleasant and affable patients may become irritable and verbally abusive, demanding medications. Patients may describe thirst so intense that they drink surreptitiously from toilet bowls. They may engage in a guzzle-and-vomit sequence that can be mistaken for bulimia, and which may actually be explained by the transient relief provided by sudden emptying of the stomach.

Other patients may ask for repeated hot showers or baths. Some patients may appear so immobile that it is difficult to establish whether they are asleep or awake; they also may withdraw from social contact, a frightening condition Dr. Fleisher describes as “conscious coma.”

CVS patients often undergo batteries of tests, including upper GI series, abdominal ultrasound and CT scan, colonoscopy, barium enema, endoscopy, MRI of the head, sinus radiography, EEG, and lab work, usually with negative results.

In Dr. Fleisher's series, the 41 patients underwent almost 300 diagnostic studies—none of which were indicative of an organic etiology for CVS. Recent findings suggest that about 75% of patients with CVS show rapid gastric emptying on electrogastrograms, and this may help distinguish CVS from other vomiting disorders (Neurogastroenterol. Motil. 2006;18:728 [abstract 200]).

Unnecessary surgeries are also common. Of the 41 patients in the series, 10 had undergone cholecystectomies, 2 had appendectomies, 5 had laparoscopies, 1 had a hysterectomy, and others had undergone other GI procedures. None of these procedures relieved the CVS symptoms.

Part of the problem is the lack of continuity of care for these patients, especially those who present repeatedly to hospital emergency departments. Dr. Fleisher suggests that more CVS centers should be created and staffed by two to three physicians available 24/7, as well as by nurses and mental health professionals. A patient can be managed routinely by his primary care physician, and then referred when necessary to a CVS center cognizant of his history, he added.

The Cyclic Vomiting Syndrome Association (www.cvsaonline.org

The average delay in making the diagnosis of CVS is 8 years from the time symptoms first appear. DR. LI

Knowledge, Patience Key to Managing the Four Phases of Cyclic Vomiting Syndrome

A physician must be knowledgeable, accessible, patient, nonjudgmental, and quick to respond when treating adults with cyclic vomiting syndrome, Dr. Fleisher said, and follow a rational treatment plan, tailored to the phase of the disease, that includes sedation when symptoms rage uncontrollably.

The CVS cycle has four phases, said Dr. Fleisher, who has treated more than 350 pediatric and adult CVS patients at the University of Missouri Hospital and Clinics, Columbia. The time between episodes, when the patient is feeling well, can be considered the first phase. The goal in this phase is to prevent a CVS episode by recognizing and controlling triggers, such as menstruation, noxious stress, pleasant excitement, fatigue, or infection. Some patients have interepisodic dyspeptic nausea and abdominal discomfort, especially in the mornings, and they may respond to proton-pump inhibitors.

The physician should help the patient regain a sense of being in control, rather than being at the mercy of CVS symptoms; this can be critical in determining overall treatment success, he said.

Dr. Fleisher considers CVS to be a manifestation of migraine diathesis in some patients. In a group of 41 adults with CVS, 70% had migraines during or between episodes, and 57% had first- and/or second-degree relatives with migraines. For these patients, migraine prophylaxis is essential to prevent CVS symptoms.

For two-thirds of Dr. Fleisher's group, severe anxiety and panic attacks triggered CVS episodes, and the panic symptoms persisted for hours or days. He likens the symptoms to those of an “adrenergic storm” seen in patients with pheochromocytoma. Patients begin to fall into a vicious cycle of anticipatory anxiety, whereby the worry about having a CVS episode increases the likelihood of another attack.

Some CVS patients have a propensity to both migraines and anxiety/panic attacks. A careful medical history can help physicians recognize the pathogenic factors specific for each patient, leading to an appropriate preventive strategy.

In the prodromal phase, the physician and patient have the chance to abort the emetic phase. In Dr. Fleisher's group, 93% had recognizable prodromes; common symptoms included nausea, sweating, epigastric pain or pressure, fatigue or weakness, feeling hot or cold, cramping urge to defecate, abdominal pain, shivering or shakiness, insomnia, food aversion, palpitations, irritability, and panic.

Depending on the symptom, appropriate medications during the prodrome include lorazepam, alprazolam, and/or ondansetron orally or sublingually for nausea, analgesics for abdominal pain, antianxiety medications for anxiety, and a triptan for headaches. Sleep may also be beneficial.

During the emetic phase, the goal is to rapidly terminate the episode, preferably within 1 hour of onset. In a sample of 39 adults with CVS, more than half had vomiting episodes lasting 3 days or more. Steps to take include prevention or correction of dehydration with IV fluids, and IV administration of antiemetics, antianxiolytic agents, and H2-receptor blockers or proton-pump inhibitors. In some cases, IV opiates are necessary for pain control. Patients should be checked for electrolyte depletion, tetany, hematemesis, and secretion of inappropriate antidiuretic hormone.

If the CVS episode cannot be terminated, Dr. Fleisher recommends sedating the patient in a dimly lit and quiet room until the episode passes. “A CVS patient needs to know there is an escape hatch that gets them out of their misery. Without that, the more they will suffer and the more they will coalesce,” Dr. Fleisher said, referring to the process in which CVS episodes become more and more frequent. He recommends chlorpromazine (0.5–1.0 mg/kg) plus diphenhydramine (0.5–1.0 mg/kg) in normal saline over 15 minutes, which can be repeated as often as every 3–4 hours if needed.

The duration of the recovery period reflects the adequacy of management of the emetic phase. Patients with severe fluid or electrolyte deficits will have a more difficult and prolonged recovery. Some patients can tolerate a normal diet soon after the emetic phase passes, while others will tolerate only clear liquids.

“Long waits in emergency rooms, encounters with caregivers who are unfamiliar with CVS, receiving implausible diagnoses, the repetition of unrewarding diagnostic procedures, and stopgap intravenous hydration followed by being sent home still sick are common experiences that reinforce patients' feelings of being out of control of an illness that no one understands or can treat,” Dr. Fleisher wrote in a 2005 report on the 41 patients (see

www.biomedcentral.com/1741-7015/3/20

ATLANTA — Children who stutter have been found to have deficiencies in white-matter organization in a tract that interconnects the frontal speech/motor planning region and the posterior speech comprehension region, suggesting that inefficient connectivity among speech-relevant regions of the left hemisphere may be a possible neuroanatomical basis for stuttering, Soo-Eun Chang, Ph.D., reported in a poster at the annual meeting of the Society for Neuroscience.

Adults who stutter show the same tract abnormalities as do children, but, in addition, they show asymmetry in gray-matter volume, suggesting that the gray-matter findings in adults reflect neuroplastic changes secondary to a lifetime of stuttering.

“What this shows is that the adult studies are compromised because there are two things going on: the original deficit, and then the neuroplasticity that is laid on top of that, “Christy L. Ludlow, Ph.D., section chief of the National Institute of Neurological Disorders and Stroke and a coauthor of the study, said in an interview. This gives us a clear picture of what the actual deficit is.”

In their study, 22 monolingual, right-handed boys aged 9–12 years underwent high-resolution, diffusion-weighted imaging (DWI) MRI studies.

The study children fell into three subgroups: normal fluent controls (seven), children who showed persistent stuttering (eight), and children who previously stuttered but had recovered and had been fluent for at least 2 years prior to scanning (seven).

Fractional anisotropy maps were calculated for each subject to delineate tracts; tract-based spatial statistics were also calculated, and regions of interest were analyzed.

When compared with normal controls, children who stutter had reduced white-matter integrity only in the left arcuate fasciculus (a tract that underlies the oral-facial motor regions), as measured by fractional anisotropy.

Studies by other investigators have shown that stuttering adults manifest increased gray-matter volume in the right hemisphere, whereas fluent adults show greater left hemisphere volume.

However, no such gray-matter asymmetry could be found in children, the investigators noted. “In fact, they show less volume in both sides of the brain in speech areas,” which suggests that the initial deficit is different from what people see in adults, said Dr. Ludlow.

The left rolandic operculum fractional anisotropy abnormality was not related to ongoing stuttering, because no difference was found in this region between the brains of children who recovered and those of children who continued to stutter.

The abnormality indicates a risk for stuttering, not whether there is a chance of recovery from stuttering. “This is a novel finding because there haven't been any studies to date looking at the brains of children who stutter. There have only been studies of adults who stutter,” she said.

“Our research suggests that some of the brain-imaging differences found in stuttering adults may be the result of a lifetime of coping with stuttering,” she said.

Findings in stuttering adults may reflect neuroplastic changes from a lifetime of stuttering. DR. CHANG

Children with stuttering (both persistent and recovered) had significantly less fractional anisotropy, a measure of white- matter integrity, in rolandic operculum than controls on DWI MRI studies. Courtesy Dr. Soo-Eun Chang

ATLANTA — Children who stutter have been found to have deficiencies in white-matter organization in a tract that interconnects the frontal speech/motor planning region and the posterior speech comprehension region, suggesting that inefficient connectivity among speech-relevant regions of the left hemisphere may be a possible neuroanatomical basis for stuttering, Soo-Eun Chang, Ph.D., reported in a poster at the annual meeting of the Society for Neuroscience.

Adults who stutter show the same tract abnormalities as do children, but, in addition, they show asymmetry in gray-matter volume, suggesting that the gray-matter findings in adults reflect neuroplastic changes secondary to a lifetime of stuttering.

“What this shows is that the adult studies are compromised because there are two things going on: the original deficit, and then the neuroplasticity that is laid on top of that, “Christy L. Ludlow, Ph.D., section chief of the National Institute of Neurological Disorders and Stroke and a coauthor of the study, said in an interview. This gives us a clear picture of what the actual deficit is.”

In their study, 22 monolingual, right-handed boys aged 9–12 years underwent high-resolution, diffusion-weighted imaging (DWI) MRI studies.

The study children fell into three subgroups: normal fluent controls (seven), children who showed persistent stuttering (eight), and children who previously stuttered but had recovered and had been fluent for at least 2 years prior to scanning (seven).

Fractional anisotropy maps were calculated for each subject to delineate tracts; tract-based spatial statistics were also calculated, and regions of interest were analyzed.

When compared with normal controls, children who stutter had reduced white-matter integrity only in the left arcuate fasciculus (a tract that underlies the oral-facial motor regions), as measured by fractional anisotropy.

Studies by other investigators have shown that stuttering adults manifest increased gray-matter volume in the right hemisphere, whereas fluent adults show greater left hemisphere volume.

However, no such gray-matter asymmetry could be found in children, the investigators noted. “In fact, they show less volume in both sides of the brain in speech areas,” which suggests that the initial deficit is different from what people see in adults, said Dr. Ludlow.

The left rolandic operculum fractional anisotropy abnormality was not related to ongoing stuttering, because no difference was found in this region between the brains of children who recovered and those of children who continued to stutter.

The abnormality indicates a risk for stuttering, not whether there is a chance of recovery from stuttering. “This is a novel finding because there haven't been any studies to date looking at the brains of children who stutter. There have only been studies of adults who stutter,” she said.

“Our research suggests that some of the brain-imaging differences found in stuttering adults may be the result of a lifetime of coping with stuttering,” she said.

Findings in stuttering adults may reflect neuroplastic changes from a lifetime of stuttering. DR. CHANG

Children with stuttering (both persistent and recovered) had significantly less fractional anisotropy, a measure of white- matter integrity, in rolandic operculum than controls on DWI MRI studies. Courtesy Dr. Soo-Eun Chang

ATLANTA — Children who stutter have been found to have deficiencies in white-matter organization in a tract that interconnects the frontal speech/motor planning region and the posterior speech comprehension region, suggesting that inefficient connectivity among speech-relevant regions of the left hemisphere may be a possible neuroanatomical basis for stuttering, Soo-Eun Chang, Ph.D., reported in a poster at the annual meeting of the Society for Neuroscience.

Adults who stutter show the same tract abnormalities as do children, but, in addition, they show asymmetry in gray-matter volume, suggesting that the gray-matter findings in adults reflect neuroplastic changes secondary to a lifetime of stuttering.

“What this shows is that the adult studies are compromised because there are two things going on: the original deficit, and then the neuroplasticity that is laid on top of that, “Christy L. Ludlow, Ph.D., section chief of the National Institute of Neurological Disorders and Stroke and a coauthor of the study, said in an interview. This gives us a clear picture of what the actual deficit is.”

In their study, 22 monolingual, right-handed boys aged 9–12 years underwent high-resolution, diffusion-weighted imaging (DWI) MRI studies.

The study children fell into three subgroups: normal fluent controls (seven), children who showed persistent stuttering (eight), and children who previously stuttered but had recovered and had been fluent for at least 2 years prior to scanning (seven).

Fractional anisotropy maps were calculated for each subject to delineate tracts; tract-based spatial statistics were also calculated, and regions of interest were analyzed.

When compared with normal controls, children who stutter had reduced white-matter integrity only in the left arcuate fasciculus (a tract that underlies the oral-facial motor regions), as measured by fractional anisotropy.

Studies by other investigators have shown that stuttering adults manifest increased gray-matter volume in the right hemisphere, whereas fluent adults show greater left hemisphere volume.

However, no such gray-matter asymmetry could be found in children, the investigators noted. “In fact, they show less volume in both sides of the brain in speech areas,” which suggests that the initial deficit is different from what people see in adults, said Dr. Ludlow.

The left rolandic operculum fractional anisotropy abnormality was not related to ongoing stuttering, because no difference was found in this region between the brains of children who recovered and those of children who continued to stutter.

The abnormality indicates a risk for stuttering, not whether there is a chance of recovery from stuttering. “This is a novel finding because there haven't been any studies to date looking at the brains of children who stutter. There have only been studies of adults who stutter,” she said.

“Our research suggests that some of the brain-imaging differences found in stuttering adults may be the result of a lifetime of coping with stuttering,” she said.

Findings in stuttering adults may reflect neuroplastic changes from a lifetime of stuttering. DR. CHANG

Children with stuttering (both persistent and recovered) had significantly less fractional anisotropy, a measure of white- matter integrity, in rolandic operculum than controls on DWI MRI studies. Courtesy Dr. Soo-Eun Chang

ATLANTA – Simvastatin use for at least 7 months reduced the incidence of Alzheimer's disease by 30% and Parkinson's disease by 24% in older people, according to an analysis of a Department of Veterans Affairs pharmaceutical database.

Neither lovastatin nor atorvastatin provided similar benefits.

The protective effects of simvastatin were more prominent in people without hypertension. In this subgroup, Alzheimer's incidence was reduced by 76% and the incidence of Parkinson's disease was reduced by 65%, the study's lead investigator Dr. Benjamin Wolozin reported at the annual meeting of the Society for Neuroscience.

Dr. Wolozin, professor of pharmacology at Boston University, analyzed data from a large VA pharmaceutical database that included 4.5 million patients and more than 110 million annual medication prescriptions. Individuals were excluded if they were less than 65 years of age or had a pre-existing diagnosis of senile dementia of the Alzheimer's type.

The incidence of Alzheimer's disease among patients taking statins was compared with the incidence among patients who were not taking statins. After adjustment for age, cardiovascular disease, hypertension, and diabetes, only simvastatin use significantly lowered the incidence of Alzheimer's disease (hazard ratio 0.694).

Two different mechanisms might explain the unique effects of simvastatin, compared with those of the other two statins analyzed, Dr. Wolozin said. For atorvastatin, the inability to cross the blood-brain barrier may explain its ineffectiveness.

Lovastatin and simvastatin both reduce inflammation, explained Dr. Wolozin. Only simvastatin, however, inhibits cholesterol strongly enough to reduce inflammation sufficiently to protect against Alzheimer's or Parkinson's disease.

ATLANTA – Simvastatin use for at least 7 months reduced the incidence of Alzheimer's disease by 30% and Parkinson's disease by 24% in older people, according to an analysis of a Department of Veterans Affairs pharmaceutical database.

Neither lovastatin nor atorvastatin provided similar benefits.

The protective effects of simvastatin were more prominent in people without hypertension. In this subgroup, Alzheimer's incidence was reduced by 76% and the incidence of Parkinson's disease was reduced by 65%, the study's lead investigator Dr. Benjamin Wolozin reported at the annual meeting of the Society for Neuroscience.

Dr. Wolozin, professor of pharmacology at Boston University, analyzed data from a large VA pharmaceutical database that included 4.5 million patients and more than 110 million annual medication prescriptions. Individuals were excluded if they were less than 65 years of age or had a pre-existing diagnosis of senile dementia of the Alzheimer's type.

The incidence of Alzheimer's disease among patients taking statins was compared with the incidence among patients who were not taking statins. After adjustment for age, cardiovascular disease, hypertension, and diabetes, only simvastatin use significantly lowered the incidence of Alzheimer's disease (hazard ratio 0.694).

Two different mechanisms might explain the unique effects of simvastatin, compared with those of the other two statins analyzed, Dr. Wolozin said. For atorvastatin, the inability to cross the blood-brain barrier may explain its ineffectiveness.

Lovastatin and simvastatin both reduce inflammation, explained Dr. Wolozin. Only simvastatin, however, inhibits cholesterol strongly enough to reduce inflammation sufficiently to protect against Alzheimer's or Parkinson's disease.

ATLANTA – Simvastatin use for at least 7 months reduced the incidence of Alzheimer's disease by 30% and Parkinson's disease by 24% in older people, according to an analysis of a Department of Veterans Affairs pharmaceutical database.

Neither lovastatin nor atorvastatin provided similar benefits.

The protective effects of simvastatin were more prominent in people without hypertension. In this subgroup, Alzheimer's incidence was reduced by 76% and the incidence of Parkinson's disease was reduced by 65%, the study's lead investigator Dr. Benjamin Wolozin reported at the annual meeting of the Society for Neuroscience.

Dr. Wolozin, professor of pharmacology at Boston University, analyzed data from a large VA pharmaceutical database that included 4.5 million patients and more than 110 million annual medication prescriptions. Individuals were excluded if they were less than 65 years of age or had a pre-existing diagnosis of senile dementia of the Alzheimer's type.

The incidence of Alzheimer's disease among patients taking statins was compared with the incidence among patients who were not taking statins. After adjustment for age, cardiovascular disease, hypertension, and diabetes, only simvastatin use significantly lowered the incidence of Alzheimer's disease (hazard ratio 0.694).

Two different mechanisms might explain the unique effects of simvastatin, compared with those of the other two statins analyzed, Dr. Wolozin said. For atorvastatin, the inability to cross the blood-brain barrier may explain its ineffectiveness.

Lovastatin and simvastatin both reduce inflammation, explained Dr. Wolozin. Only simvastatin, however, inhibits cholesterol strongly enough to reduce inflammation sufficiently to protect against Alzheimer's or Parkinson's disease.

ATLANTA – Fast fluid-attenuated inversion-recovery MR images reveal that the brains of patients with Alzheimer's disease show more extensive areas of focal white matter hyperintensities than do those of normal controls, and the extent of pathology is inversely correlated with cognitive performance, said Michael D. Devous, Ph.D., of the University of Texas Southwestern Medical Center at Dallas.

This new evidence strengthens the link between Alzheimer's disease and cerebrovascular pathology, he said in a poster presentation at the annual meeting of the Society for Neuroscience.

The white matter hyperintensities, also known as leukoaraiosis, are thought to be a consequence of cerebral small vessel disease.

By calculating the ratio of the volume of the white matter hyperintensities to whole brain volume (the leukoaraiosis index), physicians may be able to identify Alzheimer's patients at higher risk of rapid progression or those who are unlikely to respond well to treatment, Mitali Bose, a graduate student at the University of Texas at Dallas and a coauthor, said in an interview.

The mean leukoaraiosis index was almost twice as high in the Alzheimer's group (n = 30) than in the normal control group (n = 40) (1 ± 0.9 vs. 0.6 ± 0.7, P = .01). Total leukoaraiosis volume was also significantly higher in the Alzheimer's group than in controls (14 ± 11 vs. 6 ± 9, P = .01) while whole brain volume was significantly lower in patients than in controls (1,100 ± 107 vs. 1,164 ± 112, P =.01).

Alzheimer's patients with higher leukoaraiosis index scores were more likely to have poorer cognition, as measured with the Mini Mental State Examination (r = −0.28, P less than .05). “While this correlation was modest, it suggests an impact of leukoaraiosis on a coarse measure of general cognitive status. It is possible that correlating the specific neuroanatomical sites of leukoaraiosis with a more refined neuropsychological variable may provide additional insight into the effect of this abnormality on patient cognition,” said Dr. Devous, director of the Neuroimaging Core of the Alzheimer's Disease Center, UT Southwestern Medical Center.

The researchers also compared leukoaraiosis index scores to creatinine levels, another marker of vascular risk, and found a significant positive correlation between the two indicators (r = 0.35, P less than .01). “We still don't know the exact pathology underlying leukoaraiosis as seen on FLAIR MRI, but if [ongoing work finds that] there is correlation with pathological findings on postmortem brain, it may help us relate the leukoaraiosis to other vascular risk factors. Of course, a main goal of this work is to understand this and other risk factors as predictors of symptom severity, disease progression, and response to therapy,” Dr. Devous said in an interview.

“This is semiautomated software so it is at the first level of application. It should have clinical application once the tool is totally automated,” said Ms. Bose. The group is now exploring whether hyperintensities in the periventricular or deep subcortical areas have differential prognostic value.

'We still don't know the exact pathology underlying leukoaraiosis as seen on' MRI. DR. DEVOUS

Subcortical and periventricular areas of hyperintensities are seen in this fluid-attentuated inversion-recovery MR image. Courtesy Dr. Michael D. Devous

ATLANTA – Fast fluid-attenuated inversion-recovery MR images reveal that the brains of patients with Alzheimer's disease show more extensive areas of focal white matter hyperintensities than do those of normal controls, and the extent of pathology is inversely correlated with cognitive performance, said Michael D. Devous, Ph.D., of the University of Texas Southwestern Medical Center at Dallas.

This new evidence strengthens the link between Alzheimer's disease and cerebrovascular pathology, he said in a poster presentation at the annual meeting of the Society for Neuroscience.

The white matter hyperintensities, also known as leukoaraiosis, are thought to be a consequence of cerebral small vessel disease.

By calculating the ratio of the volume of the white matter hyperintensities to whole brain volume (the leukoaraiosis index), physicians may be able to identify Alzheimer's patients at higher risk of rapid progression or those who are unlikely to respond well to treatment, Mitali Bose, a graduate student at the University of Texas at Dallas and a coauthor, said in an interview.

The mean leukoaraiosis index was almost twice as high in the Alzheimer's group (n = 30) than in the normal control group (n = 40) (1 ± 0.9 vs. 0.6 ± 0.7, P = .01). Total leukoaraiosis volume was also significantly higher in the Alzheimer's group than in controls (14 ± 11 vs. 6 ± 9, P = .01) while whole brain volume was significantly lower in patients than in controls (1,100 ± 107 vs. 1,164 ± 112, P =.01).

Alzheimer's patients with higher leukoaraiosis index scores were more likely to have poorer cognition, as measured with the Mini Mental State Examination (r = −0.28, P less than .05). “While this correlation was modest, it suggests an impact of leukoaraiosis on a coarse measure of general cognitive status. It is possible that correlating the specific neuroanatomical sites of leukoaraiosis with a more refined neuropsychological variable may provide additional insight into the effect of this abnormality on patient cognition,” said Dr. Devous, director of the Neuroimaging Core of the Alzheimer's Disease Center, UT Southwestern Medical Center.

The researchers also compared leukoaraiosis index scores to creatinine levels, another marker of vascular risk, and found a significant positive correlation between the two indicators (r = 0.35, P less than .01). “We still don't know the exact pathology underlying leukoaraiosis as seen on FLAIR MRI, but if [ongoing work finds that] there is correlation with pathological findings on postmortem brain, it may help us relate the leukoaraiosis to other vascular risk factors. Of course, a main goal of this work is to understand this and other risk factors as predictors of symptom severity, disease progression, and response to therapy,” Dr. Devous said in an interview.

“This is semiautomated software so it is at the first level of application. It should have clinical application once the tool is totally automated,” said Ms. Bose. The group is now exploring whether hyperintensities in the periventricular or deep subcortical areas have differential prognostic value.

'We still don't know the exact pathology underlying leukoaraiosis as seen on' MRI. DR. DEVOUS

Subcortical and periventricular areas of hyperintensities are seen in this fluid-attentuated inversion-recovery MR image. Courtesy Dr. Michael D. Devous

ATLANTA – Fast fluid-attenuated inversion-recovery MR images reveal that the brains of patients with Alzheimer's disease show more extensive areas of focal white matter hyperintensities than do those of normal controls, and the extent of pathology is inversely correlated with cognitive performance, said Michael D. Devous, Ph.D., of the University of Texas Southwestern Medical Center at Dallas.

This new evidence strengthens the link between Alzheimer's disease and cerebrovascular pathology, he said in a poster presentation at the annual meeting of the Society for Neuroscience.

The white matter hyperintensities, also known as leukoaraiosis, are thought to be a consequence of cerebral small vessel disease.

By calculating the ratio of the volume of the white matter hyperintensities to whole brain volume (the leukoaraiosis index), physicians may be able to identify Alzheimer's patients at higher risk of rapid progression or those who are unlikely to respond well to treatment, Mitali Bose, a graduate student at the University of Texas at Dallas and a coauthor, said in an interview.

The mean leukoaraiosis index was almost twice as high in the Alzheimer's group (n = 30) than in the normal control group (n = 40) (1 ± 0.9 vs. 0.6 ± 0.7, P = .01). Total leukoaraiosis volume was also significantly higher in the Alzheimer's group than in controls (14 ± 11 vs. 6 ± 9, P = .01) while whole brain volume was significantly lower in patients than in controls (1,100 ± 107 vs. 1,164 ± 112, P =.01).

Alzheimer's patients with higher leukoaraiosis index scores were more likely to have poorer cognition, as measured with the Mini Mental State Examination (r = −0.28, P less than .05). “While this correlation was modest, it suggests an impact of leukoaraiosis on a coarse measure of general cognitive status. It is possible that correlating the specific neuroanatomical sites of leukoaraiosis with a more refined neuropsychological variable may provide additional insight into the effect of this abnormality on patient cognition,” said Dr. Devous, director of the Neuroimaging Core of the Alzheimer's Disease Center, UT Southwestern Medical Center.

The researchers also compared leukoaraiosis index scores to creatinine levels, another marker of vascular risk, and found a significant positive correlation between the two indicators (r = 0.35, P less than .01). “We still don't know the exact pathology underlying leukoaraiosis as seen on FLAIR MRI, but if [ongoing work finds that] there is correlation with pathological findings on postmortem brain, it may help us relate the leukoaraiosis to other vascular risk factors. Of course, a main goal of this work is to understand this and other risk factors as predictors of symptom severity, disease progression, and response to therapy,” Dr. Devous said in an interview.

“This is semiautomated software so it is at the first level of application. It should have clinical application once the tool is totally automated,” said Ms. Bose. The group is now exploring whether hyperintensities in the periventricular or deep subcortical areas have differential prognostic value.

'We still don't know the exact pathology underlying leukoaraiosis as seen on' MRI. DR. DEVOUS

Subcortical and periventricular areas of hyperintensities are seen in this fluid-attentuated inversion-recovery MR image. Courtesy Dr. Michael D. Devous