Amy Rothman Schonfeld

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, especially hypokalemia, may accompany the GI symptoms.

Patients often have 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 vomiting and abdominal pain, may be misdiagnosed 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 the 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 common as well. Of the 41 patients in Dr. Fleisher's 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 is 8 years from the time symptoms first appear. DR. LI

Treatment Options for Adult CVS

A physician must be knowledgeable, accessible, patient, nonjudgmental, and quick to respond when treating adults with cyclic vomiting syndrome, Dr. Fleisher said.

The physician should follow a rational treatment plan, tailored to the phase of the disease, that includes sedation when symptoms rage uncontrollably, he advised.

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 the feeling of being in control, rather than being at the whim 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. Dr. Fleisher 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 that lasted 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 length 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 his 2005 report on the 41 adult patients (see

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

He urges physicians to develop a working collaboration with each patient to ascertain what exacerbates and controls CVS symptoms for that individual.

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, especially hypokalemia, may accompany the GI symptoms.

Patients often have 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 vomiting and abdominal pain, may be misdiagnosed 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 the 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 common as well. Of the 41 patients in Dr. Fleisher's 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 is 8 years from the time symptoms first appear. DR. LI

Treatment Options for Adult CVS

A physician must be knowledgeable, accessible, patient, nonjudgmental, and quick to respond when treating adults with cyclic vomiting syndrome, Dr. Fleisher said.

The physician should follow a rational treatment plan, tailored to the phase of the disease, that includes sedation when symptoms rage uncontrollably, he advised.

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 the feeling of being in control, rather than being at the whim 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. Dr. Fleisher 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 that lasted 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 length 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 his 2005 report on the 41 adult patients (see

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

He urges physicians to develop a working collaboration with each patient to ascertain what exacerbates and controls CVS symptoms for that individual.

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, especially hypokalemia, may accompany the GI symptoms.

Patients often have 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 vomiting and abdominal pain, may be misdiagnosed 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 the 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 common as well. Of the 41 patients in Dr. Fleisher's 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 is 8 years from the time symptoms first appear. DR. LI

Treatment Options for Adult CVS

A physician must be knowledgeable, accessible, patient, nonjudgmental, and quick to respond when treating adults with cyclic vomiting syndrome, Dr. Fleisher said.

The physician should follow a rational treatment plan, tailored to the phase of the disease, that includes sedation when symptoms rage uncontrollably, he advised.

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 the feeling of being in control, rather than being at the whim 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. Dr. Fleisher 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 that lasted 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 length 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 his 2005 report on the 41 adult patients (see

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

He urges physicians to develop a working collaboration with each patient to ascertain what exacerbates and controls CVS symptoms for that individual.

BOSTON — Weight loss in an overweight or obese person taking sibutramine may be governed by whether the individual has a particular genotype related to the regulation of endogenous serotonin reuptake, Ms. Maria Vazquez Roque proposed at a meeting on neurogastroenterology and motility.

Sibutramine, a noradrenergic and serotonergic reuptake inhibitor, is one of two FDA-approved medications for the long-term treatment of obesity. One drawback to its use is the wide variability in response to the drug among various individuals. Investigators such as Ms. Vazquez Roque are now applying pharmacogenomics to unravel the genetic underpinnings of the differences in individuals' reactions to, or metabolism of, drugs affecting the GI system.

In her study, Ms. Vazquez Roque, who is a master's degree candidate in clinical research at Mayo Graduate School in Rochester, Minn., and her colleagues randomly assigned 24 overweight and 24 obese individuals (as determined by body mass index) to receive sibutramine (15 mg/day) or placebo for 12 weeks.

The investigators conducted DNA analyses of blood samples from the patients to determine whether the patients' responses to sibutramine correlated with the polymorphisms of a number of candidate genes related to serotonin and norepinephrine. These included SERT-P (also known as SLC6A4), the promoter region of the serotonin transporter protein; á-2 MspI, a promoter for the á-2A adrenergic receptor; phenylethanolamine-N-methyl transferase (PNMT), the enzyme that converts norepinephrine to epinephrine; and GN3 C825T, which modulates ligand-receptor interactions.

Only one genotype could be correlated with a differential response to sibutramine. Patients with the SERT-P LS/SS (heterozygous/short) genotype lost an average of 6.1 kg (plus or minus 1.0 kg), significantly more than the 0.1 kg (plus or minus 0.9 kg) weight gain of the placebo group.

Patients who were homozygous for the SERT-P LL (long) genotype showed moderate weight loss with sibutramine that was comparable with the weight loss observed with placebo. No other candidate gene showed a variable response to sibutramine.

“It is conceivable that having the LS/SS genotype enhances the effect of sibutramine, leading to greater inhibition of serotonin reuptake, leading to higher concentration of serotonin at the synapse, and greater ligand/receptor interaction in hypothalamic nuclei,” said Ms. Vazquez Roque. The ventromedial and paraventricular nuclei of the hypothalamus are thought to have a role in central appetite regulation.

“The data are preliminary, but if confirmed, they could point to a way of selecting patients who are more likely to respond to sibutramine,” said Dr. Michael Camilleri, professor of medicine and physiology at Mayo Medical School, Rochester, Minn., and a coauthor of the abstract.

In a separate presentation, Dr. Camilleri reviewed other examples of genetic influences on the response to drugs that affect the GI system, as well as GI symptomatology. For instance, patients with homozygous polymorphism of SERT show an enhanced response to alosetron, a 5HT-3 antagonist that is used in women with severe, diarrhea-predominant IBS (Gastroenterology 2002;123:425–32). Dr. Camilleri recently found that the CC genotype of GN3 is also associated with a predisposition to developing meal-unrelated dyspepsia (Am. J. Gastroenterol. 2006;101:581–92).

Last year, the Food and Drug Administration approved a DNA chip-based test, the AmpliChip CYP450 (Roche Diagnostics), which helps physicians establish a patient's genotype regarding 2D6 and 2C19 polymorphisms before initiating therapy. “It is now possible to understand the underlying genetic status of your patient and perhaps individualize dose or select a drug based on underlying genotype. We are moving more toward individualized medicine,” Dr. Camilleri said.

It is now possible to understand the underlying genetic status of a patient and perhaps individualize dose. DR. CAMILLERI

BOSTON — Weight loss in an overweight or obese person taking sibutramine may be governed by whether the individual has a particular genotype related to the regulation of endogenous serotonin reuptake, Ms. Maria Vazquez Roque proposed at a meeting on neurogastroenterology and motility.

Sibutramine, a noradrenergic and serotonergic reuptake inhibitor, is one of two FDA-approved medications for the long-term treatment of obesity. One drawback to its use is the wide variability in response to the drug among various individuals. Investigators such as Ms. Vazquez Roque are now applying pharmacogenomics to unravel the genetic underpinnings of the differences in individuals' reactions to, or metabolism of, drugs affecting the GI system.

In her study, Ms. Vazquez Roque, who is a master's degree candidate in clinical research at Mayo Graduate School in Rochester, Minn., and her colleagues randomly assigned 24 overweight and 24 obese individuals (as determined by body mass index) to receive sibutramine (15 mg/day) or placebo for 12 weeks.

The investigators conducted DNA analyses of blood samples from the patients to determine whether the patients' responses to sibutramine correlated with the polymorphisms of a number of candidate genes related to serotonin and norepinephrine. These included SERT-P (also known as SLC6A4), the promoter region of the serotonin transporter protein; á-2 MspI, a promoter for the á-2A adrenergic receptor; phenylethanolamine-N-methyl transferase (PNMT), the enzyme that converts norepinephrine to epinephrine; and GN3 C825T, which modulates ligand-receptor interactions.

Only one genotype could be correlated with a differential response to sibutramine. Patients with the SERT-P LS/SS (heterozygous/short) genotype lost an average of 6.1 kg (plus or minus 1.0 kg), significantly more than the 0.1 kg (plus or minus 0.9 kg) weight gain of the placebo group.

Patients who were homozygous for the SERT-P LL (long) genotype showed moderate weight loss with sibutramine that was comparable with the weight loss observed with placebo. No other candidate gene showed a variable response to sibutramine.

“It is conceivable that having the LS/SS genotype enhances the effect of sibutramine, leading to greater inhibition of serotonin reuptake, leading to higher concentration of serotonin at the synapse, and greater ligand/receptor interaction in hypothalamic nuclei,” said Ms. Vazquez Roque. The ventromedial and paraventricular nuclei of the hypothalamus are thought to have a role in central appetite regulation.

“The data are preliminary, but if confirmed, they could point to a way of selecting patients who are more likely to respond to sibutramine,” said Dr. Michael Camilleri, professor of medicine and physiology at Mayo Medical School, Rochester, Minn., and a coauthor of the abstract.

In a separate presentation, Dr. Camilleri reviewed other examples of genetic influences on the response to drugs that affect the GI system, as well as GI symptomatology. For instance, patients with homozygous polymorphism of SERT show an enhanced response to alosetron, a 5HT-3 antagonist that is used in women with severe, diarrhea-predominant IBS (Gastroenterology 2002;123:425–32). Dr. Camilleri recently found that the CC genotype of GN3 is also associated with a predisposition to developing meal-unrelated dyspepsia (Am. J. Gastroenterol. 2006;101:581–92).

Last year, the Food and Drug Administration approved a DNA chip-based test, the AmpliChip CYP450 (Roche Diagnostics), which helps physicians establish a patient's genotype regarding 2D6 and 2C19 polymorphisms before initiating therapy. “It is now possible to understand the underlying genetic status of your patient and perhaps individualize dose or select a drug based on underlying genotype. We are moving more toward individualized medicine,” Dr. Camilleri said.

It is now possible to understand the underlying genetic status of a patient and perhaps individualize dose. DR. CAMILLERI

BOSTON — Weight loss in an overweight or obese person taking sibutramine may be governed by whether the individual has a particular genotype related to the regulation of endogenous serotonin reuptake, Ms. Maria Vazquez Roque proposed at a meeting on neurogastroenterology and motility.

Sibutramine, a noradrenergic and serotonergic reuptake inhibitor, is one of two FDA-approved medications for the long-term treatment of obesity. One drawback to its use is the wide variability in response to the drug among various individuals. Investigators such as Ms. Vazquez Roque are now applying pharmacogenomics to unravel the genetic underpinnings of the differences in individuals' reactions to, or metabolism of, drugs affecting the GI system.

In her study, Ms. Vazquez Roque, who is a master's degree candidate in clinical research at Mayo Graduate School in Rochester, Minn., and her colleagues randomly assigned 24 overweight and 24 obese individuals (as determined by body mass index) to receive sibutramine (15 mg/day) or placebo for 12 weeks.

The investigators conducted DNA analyses of blood samples from the patients to determine whether the patients' responses to sibutramine correlated with the polymorphisms of a number of candidate genes related to serotonin and norepinephrine. These included SERT-P (also known as SLC6A4), the promoter region of the serotonin transporter protein; á-2 MspI, a promoter for the á-2A adrenergic receptor; phenylethanolamine-N-methyl transferase (PNMT), the enzyme that converts norepinephrine to epinephrine; and GN3 C825T, which modulates ligand-receptor interactions.

Only one genotype could be correlated with a differential response to sibutramine. Patients with the SERT-P LS/SS (heterozygous/short) genotype lost an average of 6.1 kg (plus or minus 1.0 kg), significantly more than the 0.1 kg (plus or minus 0.9 kg) weight gain of the placebo group.

Patients who were homozygous for the SERT-P LL (long) genotype showed moderate weight loss with sibutramine that was comparable with the weight loss observed with placebo. No other candidate gene showed a variable response to sibutramine.

“It is conceivable that having the LS/SS genotype enhances the effect of sibutramine, leading to greater inhibition of serotonin reuptake, leading to higher concentration of serotonin at the synapse, and greater ligand/receptor interaction in hypothalamic nuclei,” said Ms. Vazquez Roque. The ventromedial and paraventricular nuclei of the hypothalamus are thought to have a role in central appetite regulation.

“The data are preliminary, but if confirmed, they could point to a way of selecting patients who are more likely to respond to sibutramine,” said Dr. Michael Camilleri, professor of medicine and physiology at Mayo Medical School, Rochester, Minn., and a coauthor of the abstract.

In a separate presentation, Dr. Camilleri reviewed other examples of genetic influences on the response to drugs that affect the GI system, as well as GI symptomatology. For instance, patients with homozygous polymorphism of SERT show an enhanced response to alosetron, a 5HT-3 antagonist that is used in women with severe, diarrhea-predominant IBS (Gastroenterology 2002;123:425–32). Dr. Camilleri recently found that the CC genotype of GN3 is also associated with a predisposition to developing meal-unrelated dyspepsia (Am. J. Gastroenterol. 2006;101:581–92).

Last year, the Food and Drug Administration approved a DNA chip-based test, the AmpliChip CYP450 (Roche Diagnostics), which helps physicians establish a patient's genotype regarding 2D6 and 2C19 polymorphisms before initiating therapy. “It is now possible to understand the underlying genetic status of your patient and perhaps individualize dose or select a drug based on underlying genotype. We are moving more toward individualized medicine,” Dr. Camilleri said.

It is now possible to understand the underlying genetic status of a patient and perhaps individualize dose. DR. CAMILLERI

MONTREAL — Characteristic changes on brain MRI can help diagnose and differentiate congenital muscular dystrophies with brain and eye abnormalities, reported Dr. Jiri Vajsar.

Congenital muscular dystrophies (CMDs) with brain involvement share several common features, explained Dr. Vajsar at the 10th International Child Neurology Congress. All are autosomal recessive diseases that are characterized by early-onset hypotonia and weakness, delayed motor development, and elevated creatine kinase levels. Some CMD types also manifest mental retardation, delayed global development with subsequent regression, progressive contractures, seizures, variable ophthalmic findings, and cardiac and respiratory involvement.

Immunohistochemically, CMDs with brain involvement can be grouped into those with a deficiency in laminin-α2 chain (also known as merosin) or in α-dystroglycan, said Dr. Vajsar, a neurologist affiliated with the Hospital for Sick Children in Toronto.

MRIs of children with laminin-α2 chain deficiency show easily identifiable abnormalities in myelinated areas, although the corpus callosum and optic radiation remain normal. Despite the white matter abnormalities, these children maintain good cognitive function; however, about 30% are prone to seizures.

It is more difficult to generalize about the appearance on MRI of α-dystroglycan deficient CMDs, because several CMD phenotypes exist, said Dr. Vajsar. As a general rule, MRIs of these disorders show abnormalities in the posterior fossa, such as flattening of the pons, cerebellar hypoplasia or dysplasia, cerebellar cysts, and hypoplastic or absent vermis. The cortex takes on a cobblestone appearance, with disorganized cortical layers due to abnormal neuronal migration; multiple, abnormal, and coarse gyri with agyric regions; and variable thickness.

For example, in the most severe type of CMD, Walker-Warburg syndrome (WWS), MRI findings include type II lissencephaly (cortical smoothing) and cerebellar malformation. Ventriculomegaly and abnormalities of corpus callosum and splenium are also common. Anterior (e.g., cataracts, microcornea, microphthalmia, lens defects) or posterior (e.g., retinal detachment, optic nerve atrophy, glaucoma) eye abnormalities are also frequent. Clinically, children with WWS are profoundly retarded, have seizures, and usually succumb to death within the first 3 years of life.

MRI findings in children with other CMD types show a spectrum of generally milder gray and white matter abnormalities, said Dr. Vajsar. In muscle-eye-brain (MEB) disease, cortical, cerebellar, and callosum/splenium abnormalities are less prominent than in WWS. Polymicrogyria and thickened cortex may be noted in the frontal and parietal cortices, while agyria, cortical thinning, and lissencephaly may be evident in the occipital cortex.

MRI in patients with MDC type 1C may show normal brain with or without cerebellar cysts, said Dr. Vajsar. Occasionally, MRI shows other white and gray matter abnormalities, from cortical migrational anomalies and white matter changes to MEB-type or WWS patterns of abnormalities.

Brain MRIs can help diagnose and classify muscular dystrophies. Above, a T2 image shows abnormal high signal in white matter (left) in congenital muscular dystrophy. Smooth cortex lacks sulcation; abnormalities of the corpus callosum and cerebellum and enlarged ventricles are consistent with Walker-Warburg syndrome (middle). Thick cortex is indicative of muscle-eye-brain disease migrational abnormality (right). Photos courtesy Dr. Jiri Vajsar

MONTREAL — Characteristic changes on brain MRI can help diagnose and differentiate congenital muscular dystrophies with brain and eye abnormalities, reported Dr. Jiri Vajsar.

Congenital muscular dystrophies (CMDs) with brain involvement share several common features, explained Dr. Vajsar at the 10th International Child Neurology Congress. All are autosomal recessive diseases that are characterized by early-onset hypotonia and weakness, delayed motor development, and elevated creatine kinase levels. Some CMD types also manifest mental retardation, delayed global development with subsequent regression, progressive contractures, seizures, variable ophthalmic findings, and cardiac and respiratory involvement.

Immunohistochemically, CMDs with brain involvement can be grouped into those with a deficiency in laminin-α2 chain (also known as merosin) or in α-dystroglycan, said Dr. Vajsar, a neurologist affiliated with the Hospital for Sick Children in Toronto.

MRIs of children with laminin-α2 chain deficiency show easily identifiable abnormalities in myelinated areas, although the corpus callosum and optic radiation remain normal. Despite the white matter abnormalities, these children maintain good cognitive function; however, about 30% are prone to seizures.

It is more difficult to generalize about the appearance on MRI of α-dystroglycan deficient CMDs, because several CMD phenotypes exist, said Dr. Vajsar. As a general rule, MRIs of these disorders show abnormalities in the posterior fossa, such as flattening of the pons, cerebellar hypoplasia or dysplasia, cerebellar cysts, and hypoplastic or absent vermis. The cortex takes on a cobblestone appearance, with disorganized cortical layers due to abnormal neuronal migration; multiple, abnormal, and coarse gyri with agyric regions; and variable thickness.

For example, in the most severe type of CMD, Walker-Warburg syndrome (WWS), MRI findings include type II lissencephaly (cortical smoothing) and cerebellar malformation. Ventriculomegaly and abnormalities of corpus callosum and splenium are also common. Anterior (e.g., cataracts, microcornea, microphthalmia, lens defects) or posterior (e.g., retinal detachment, optic nerve atrophy, glaucoma) eye abnormalities are also frequent. Clinically, children with WWS are profoundly retarded, have seizures, and usually succumb to death within the first 3 years of life.

MRI findings in children with other CMD types show a spectrum of generally milder gray and white matter abnormalities, said Dr. Vajsar. In muscle-eye-brain (MEB) disease, cortical, cerebellar, and callosum/splenium abnormalities are less prominent than in WWS. Polymicrogyria and thickened cortex may be noted in the frontal and parietal cortices, while agyria, cortical thinning, and lissencephaly may be evident in the occipital cortex.

MRI in patients with MDC type 1C may show normal brain with or without cerebellar cysts, said Dr. Vajsar. Occasionally, MRI shows other white and gray matter abnormalities, from cortical migrational anomalies and white matter changes to MEB-type or WWS patterns of abnormalities.

Brain MRIs can help diagnose and classify muscular dystrophies. Above, a T2 image shows abnormal high signal in white matter (left) in congenital muscular dystrophy. Smooth cortex lacks sulcation; abnormalities of the corpus callosum and cerebellum and enlarged ventricles are consistent with Walker-Warburg syndrome (middle). Thick cortex is indicative of muscle-eye-brain disease migrational abnormality (right). Photos courtesy Dr. Jiri Vajsar

MONTREAL — Characteristic changes on brain MRI can help diagnose and differentiate congenital muscular dystrophies with brain and eye abnormalities, reported Dr. Jiri Vajsar.

Congenital muscular dystrophies (CMDs) with brain involvement share several common features, explained Dr. Vajsar at the 10th International Child Neurology Congress. All are autosomal recessive diseases that are characterized by early-onset hypotonia and weakness, delayed motor development, and elevated creatine kinase levels. Some CMD types also manifest mental retardation, delayed global development with subsequent regression, progressive contractures, seizures, variable ophthalmic findings, and cardiac and respiratory involvement.

Immunohistochemically, CMDs with brain involvement can be grouped into those with a deficiency in laminin-α2 chain (also known as merosin) or in α-dystroglycan, said Dr. Vajsar, a neurologist affiliated with the Hospital for Sick Children in Toronto.

MRIs of children with laminin-α2 chain deficiency show easily identifiable abnormalities in myelinated areas, although the corpus callosum and optic radiation remain normal. Despite the white matter abnormalities, these children maintain good cognitive function; however, about 30% are prone to seizures.

It is more difficult to generalize about the appearance on MRI of α-dystroglycan deficient CMDs, because several CMD phenotypes exist, said Dr. Vajsar. As a general rule, MRIs of these disorders show abnormalities in the posterior fossa, such as flattening of the pons, cerebellar hypoplasia or dysplasia, cerebellar cysts, and hypoplastic or absent vermis. The cortex takes on a cobblestone appearance, with disorganized cortical layers due to abnormal neuronal migration; multiple, abnormal, and coarse gyri with agyric regions; and variable thickness.

For example, in the most severe type of CMD, Walker-Warburg syndrome (WWS), MRI findings include type II lissencephaly (cortical smoothing) and cerebellar malformation. Ventriculomegaly and abnormalities of corpus callosum and splenium are also common. Anterior (e.g., cataracts, microcornea, microphthalmia, lens defects) or posterior (e.g., retinal detachment, optic nerve atrophy, glaucoma) eye abnormalities are also frequent. Clinically, children with WWS are profoundly retarded, have seizures, and usually succumb to death within the first 3 years of life.

MRI findings in children with other CMD types show a spectrum of generally milder gray and white matter abnormalities, said Dr. Vajsar. In muscle-eye-brain (MEB) disease, cortical, cerebellar, and callosum/splenium abnormalities are less prominent than in WWS. Polymicrogyria and thickened cortex may be noted in the frontal and parietal cortices, while agyria, cortical thinning, and lissencephaly may be evident in the occipital cortex.

MRI in patients with MDC type 1C may show normal brain with or without cerebellar cysts, said Dr. Vajsar. Occasionally, MRI shows other white and gray matter abnormalities, from cortical migrational anomalies and white matter changes to MEB-type or WWS patterns of abnormalities.

Brain MRIs can help diagnose and classify muscular dystrophies. Above, a T2 image shows abnormal high signal in white matter (left) in congenital muscular dystrophy. Smooth cortex lacks sulcation; abnormalities of the corpus callosum and cerebellum and enlarged ventricles are consistent with Walker-Warburg syndrome (middle). Thick cortex is indicative of muscle-eye-brain disease migrational abnormality (right). Photos courtesy Dr. Jiri Vajsar

BOSTON — Approved earlier this year for the treatment of chronic idiopathic constipation in adults, lubiprostone has been shown to provide long-term relief for elderly patients, according to the findings of an industry-sponsored study.

Constipation is the most common gastrointestinal complaint among patients with advanced age. About 24%-37% of community-dwelling elderly people are affected; an estimated 60% use laxatives. The condition is even more common among nursing home residents. Left untreated, even mild constipation can eventually lead to serious complications such as fecal impaction, incontinence, and bowel perforations, Dr. Ryuji Ueno said at a meeting on neurogastroenterology and motility.

Dr. Ueno is the chief scientific officer at Sucampo Pharmaceuticals Inc., the manufacturer of lubiprostone that funded the investigation.

Dr. Ueno and colleagues analyzed data from three open-label clinical trials involving a total of 163 elderly patients (aged 65 years and older) and 715 nonelderly patients (aged 18–64 years) who had chronic constipation, defined as fewer than three spontaneous bowel movements per week, with a minimum history of 3 months of evacuation difficulties.

Patients were excluded if they had documented mechanical obstruction and/or organic disorders of the bowel, constipation secondary to a documented cause, or other clinically significant medical conditions.

Patients were treated with oral lubiprostone (24 mcg twice daily), a type-2 chloride channel activator that promotes gastrointestinal motility by increasing the production of chloride-rich intestinal fluid, without significantly affecting serum sodium or potassium. Patients were followed for up to 12 months, with efficacy and safety assessments every 4–6 weeks.

Lubiprostone produced sustained, statistically significant improvements from baseline in constipation severity, abdominal bloating, and discomfort across the year-long observation period for both the elderly and nonelderly groups. With use of a 5-point subjective severity scale (0 = absent to 4 = very severe), the mean improvement from baseline in constipation severity ranged from 0.92 to 1.71 points, for abdominal bloating mean improvement ranged from 0.45 to 1.19 points, and for abdominal discomfort the range was 0.49–0.89 points improved.

Elderly patients appeared to tolerate lubiprostone as well or better than their younger counterparts did. The elderly group reported fewer adverse events of any sort than did the nonelderly group (74% vs. 80%). No treatment-related serious side effects occurred in an elderly person and, with the exception of diarrhea (15% elderly vs. 12% nonelderly) and loose stools (6% vs. 3%), the incidence rates of commonly reported treatment-related adverse events were lower in the elderly than in the nonelderly. For example, nausea, the most common adverse event, was reported by 29% of the younger group but only 18% of the elderly.

BOSTON — Approved earlier this year for the treatment of chronic idiopathic constipation in adults, lubiprostone has been shown to provide long-term relief for elderly patients, according to the findings of an industry-sponsored study.

Constipation is the most common gastrointestinal complaint among patients with advanced age. About 24%-37% of community-dwelling elderly people are affected; an estimated 60% use laxatives. The condition is even more common among nursing home residents. Left untreated, even mild constipation can eventually lead to serious complications such as fecal impaction, incontinence, and bowel perforations, Dr. Ryuji Ueno said at a meeting on neurogastroenterology and motility.

Dr. Ueno is the chief scientific officer at Sucampo Pharmaceuticals Inc., the manufacturer of lubiprostone that funded the investigation.

Dr. Ueno and colleagues analyzed data from three open-label clinical trials involving a total of 163 elderly patients (aged 65 years and older) and 715 nonelderly patients (aged 18–64 years) who had chronic constipation, defined as fewer than three spontaneous bowel movements per week, with a minimum history of 3 months of evacuation difficulties.

Patients were excluded if they had documented mechanical obstruction and/or organic disorders of the bowel, constipation secondary to a documented cause, or other clinically significant medical conditions.

Patients were treated with oral lubiprostone (24 mcg twice daily), a type-2 chloride channel activator that promotes gastrointestinal motility by increasing the production of chloride-rich intestinal fluid, without significantly affecting serum sodium or potassium. Patients were followed for up to 12 months, with efficacy and safety assessments every 4–6 weeks.

Lubiprostone produced sustained, statistically significant improvements from baseline in constipation severity, abdominal bloating, and discomfort across the year-long observation period for both the elderly and nonelderly groups. With use of a 5-point subjective severity scale (0 = absent to 4 = very severe), the mean improvement from baseline in constipation severity ranged from 0.92 to 1.71 points, for abdominal bloating mean improvement ranged from 0.45 to 1.19 points, and for abdominal discomfort the range was 0.49–0.89 points improved.

Elderly patients appeared to tolerate lubiprostone as well or better than their younger counterparts did. The elderly group reported fewer adverse events of any sort than did the nonelderly group (74% vs. 80%). No treatment-related serious side effects occurred in an elderly person and, with the exception of diarrhea (15% elderly vs. 12% nonelderly) and loose stools (6% vs. 3%), the incidence rates of commonly reported treatment-related adverse events were lower in the elderly than in the nonelderly. For example, nausea, the most common adverse event, was reported by 29% of the younger group but only 18% of the elderly.

BOSTON — Approved earlier this year for the treatment of chronic idiopathic constipation in adults, lubiprostone has been shown to provide long-term relief for elderly patients, according to the findings of an industry-sponsored study.

Constipation is the most common gastrointestinal complaint among patients with advanced age. About 24%-37% of community-dwelling elderly people are affected; an estimated 60% use laxatives. The condition is even more common among nursing home residents. Left untreated, even mild constipation can eventually lead to serious complications such as fecal impaction, incontinence, and bowel perforations, Dr. Ryuji Ueno said at a meeting on neurogastroenterology and motility.

Dr. Ueno is the chief scientific officer at Sucampo Pharmaceuticals Inc., the manufacturer of lubiprostone that funded the investigation.

Dr. Ueno and colleagues analyzed data from three open-label clinical trials involving a total of 163 elderly patients (aged 65 years and older) and 715 nonelderly patients (aged 18–64 years) who had chronic constipation, defined as fewer than three spontaneous bowel movements per week, with a minimum history of 3 months of evacuation difficulties.

Patients were excluded if they had documented mechanical obstruction and/or organic disorders of the bowel, constipation secondary to a documented cause, or other clinically significant medical conditions.

Patients were treated with oral lubiprostone (24 mcg twice daily), a type-2 chloride channel activator that promotes gastrointestinal motility by increasing the production of chloride-rich intestinal fluid, without significantly affecting serum sodium or potassium. Patients were followed for up to 12 months, with efficacy and safety assessments every 4–6 weeks.

Lubiprostone produced sustained, statistically significant improvements from baseline in constipation severity, abdominal bloating, and discomfort across the year-long observation period for both the elderly and nonelderly groups. With use of a 5-point subjective severity scale (0 = absent to 4 = very severe), the mean improvement from baseline in constipation severity ranged from 0.92 to 1.71 points, for abdominal bloating mean improvement ranged from 0.45 to 1.19 points, and for abdominal discomfort the range was 0.49–0.89 points improved.

Elderly patients appeared to tolerate lubiprostone as well or better than their younger counterparts did. The elderly group reported fewer adverse events of any sort than did the nonelderly group (74% vs. 80%). No treatment-related serious side effects occurred in an elderly person and, with the exception of diarrhea (15% elderly vs. 12% nonelderly) and loose stools (6% vs. 3%), the incidence rates of commonly reported treatment-related adverse events were lower in the elderly than in the nonelderly. For example, nausea, the most common adverse event, was reported by 29% of the younger group but only 18% of the elderly.

BOSTON — A new noninvasive treatment—transcutaneous electrical stimulation—may relieve symptoms for several months in children with slow transit constipation, Bridget Southwell, Ph.D., said at the Neurogastroenterology and Motility 2006 Joint International Meeting.

Imaging studies showed that slow colonic transit might be an underlying factor in about 60% of 155 children with idiopathic, treatment-resistant constipation. Children with this condition, known as slow transit constipation (STC), show deficits in propagating contractions of the colon, and fail to respond to stimuli that normally activate the gut.

The children in the study who received electrical stimulation were part of a larger group of 155 children with idiopathic, chronic, treatment-resistant constipation seen between 1995 and 2004. Children with known causes of chronic constipation, such as those with metabolic or genetic disorders, Hirschsprung's disease, or palpable fecalomas, were excluded from the study population. All of the subgroup had failed diet, laxative treatment, and behavioral therapy; the effects of constipation infringed upon school and play.

Transcutaneous stimulation using interferential current was applied for 20 minutes three times per week for 3–4 weeks using four surface electrodes, placed in front of and behind the umbilical area. Of the 16 children who received electrical stimulation, 81% showed increased defecation and 94% showed decreased soiling. The effects lasted for 3 months or more after stimulation. Dr. Southwell's work merited an Abstract of Distinction and Young Investigator Travel Award.

“Transcutaneous electrical stimulation was originally developed for bladder disorders. It has been used for more than 20 years so we know it is safe,” Dr. Southwell said in an interview. “We hope stimulation [for constipation] will develop into a technique that can be done in the home. Then it could be used by children anywhere, and also by the elderly. At the moment, it is a technique that must be done by physiotherapists.” Dr. Southwell leads a group in Gut Motility Research at the Murdoch Children's Research Institute, Royal Children's Hospital in Victoria (Australia).

The investigators used 48-hour radioisotope transit studies to follow movement through the colon and document STC. Of 155 studies, 20% showed normal transit, 20% anal retention, and 60% pancolonic slowing. (See these patterns in the illustration.)

Those with normal transit show accumulation in the cecum by 6 hours, radioactivity in the rectum by 30 hours, and no radioactivity by 48 hours because of elimination. Those with anal retention show radioactivity remaining in the rectum for 24–48 hours, whereas children with STC show radioactivity in the transverse or descending colons for 30–48 hours, at which point the rectum is still unreactive.

The researchers also evaluated neuromuscular function in children with STC by using 24-hour colonic manometry, in which a catheter with multiple recording sites spanning the colon is inserted via an appendix stoma to monitor contractions. When the results of 18 children with STC were compared with 8 non-STC children, those with STC had fewer anterior propagating contractions and showed no increase in gut activity upon awakening or after eating—findings consistent with poor contractions in the colon and slow transit constipation.

In another poster at the same meeting, Dr. Southwell's group at the Royal Children's Hospital in Victoria described findings suggesting that innervation of the gut wall may be compromised in STC. They reported lower levels of substance P and vasoactive intestinal peptide in biopsies taken from the right colon of children with STC, compared with constipated children without colonic dysmotility.

'We hope stimulation [for constipation] will develop into a technique that can be done in the home.' DR. SOUTHWELL

In 155 children, scintigraphy studies showed that about 20% had normal transit, 20% had anorectal retention, and 60% had slow colonic transit. Courtesy Dr. Bridget Southwell

BOSTON — A new noninvasive treatment—transcutaneous electrical stimulation—may relieve symptoms for several months in children with slow transit constipation, Bridget Southwell, Ph.D., said at the Neurogastroenterology and Motility 2006 Joint International Meeting.

Imaging studies showed that slow colonic transit might be an underlying factor in about 60% of 155 children with idiopathic, treatment-resistant constipation. Children with this condition, known as slow transit constipation (STC), show deficits in propagating contractions of the colon, and fail to respond to stimuli that normally activate the gut.

The children in the study who received electrical stimulation were part of a larger group of 155 children with idiopathic, chronic, treatment-resistant constipation seen between 1995 and 2004. Children with known causes of chronic constipation, such as those with metabolic or genetic disorders, Hirschsprung's disease, or palpable fecalomas, were excluded from the study population. All of the subgroup had failed diet, laxative treatment, and behavioral therapy; the effects of constipation infringed upon school and play.

Transcutaneous stimulation using interferential current was applied for 20 minutes three times per week for 3–4 weeks using four surface electrodes, placed in front of and behind the umbilical area. Of the 16 children who received electrical stimulation, 81% showed increased defecation and 94% showed decreased soiling. The effects lasted for 3 months or more after stimulation. Dr. Southwell's work merited an Abstract of Distinction and Young Investigator Travel Award.

“Transcutaneous electrical stimulation was originally developed for bladder disorders. It has been used for more than 20 years so we know it is safe,” Dr. Southwell said in an interview. “We hope stimulation [for constipation] will develop into a technique that can be done in the home. Then it could be used by children anywhere, and also by the elderly. At the moment, it is a technique that must be done by physiotherapists.” Dr. Southwell leads a group in Gut Motility Research at the Murdoch Children's Research Institute, Royal Children's Hospital in Victoria (Australia).

The investigators used 48-hour radioisotope transit studies to follow movement through the colon and document STC. Of 155 studies, 20% showed normal transit, 20% anal retention, and 60% pancolonic slowing. (See these patterns in the illustration.)

Those with normal transit show accumulation in the cecum by 6 hours, radioactivity in the rectum by 30 hours, and no radioactivity by 48 hours because of elimination. Those with anal retention show radioactivity remaining in the rectum for 24–48 hours, whereas children with STC show radioactivity in the transverse or descending colons for 30–48 hours, at which point the rectum is still unreactive.

The researchers also evaluated neuromuscular function in children with STC by using 24-hour colonic manometry, in which a catheter with multiple recording sites spanning the colon is inserted via an appendix stoma to monitor contractions. When the results of 18 children with STC were compared with 8 non-STC children, those with STC had fewer anterior propagating contractions and showed no increase in gut activity upon awakening or after eating—findings consistent with poor contractions in the colon and slow transit constipation.

In another poster at the same meeting, Dr. Southwell's group at the Royal Children's Hospital in Victoria described findings suggesting that innervation of the gut wall may be compromised in STC. They reported lower levels of substance P and vasoactive intestinal peptide in biopsies taken from the right colon of children with STC, compared with constipated children without colonic dysmotility.

'We hope stimulation [for constipation] will develop into a technique that can be done in the home.' DR. SOUTHWELL

In 155 children, scintigraphy studies showed that about 20% had normal transit, 20% had anorectal retention, and 60% had slow colonic transit. Courtesy Dr. Bridget Southwell

BOSTON — A new noninvasive treatment—transcutaneous electrical stimulation—may relieve symptoms for several months in children with slow transit constipation, Bridget Southwell, Ph.D., said at the Neurogastroenterology and Motility 2006 Joint International Meeting.

Imaging studies showed that slow colonic transit might be an underlying factor in about 60% of 155 children with idiopathic, treatment-resistant constipation. Children with this condition, known as slow transit constipation (STC), show deficits in propagating contractions of the colon, and fail to respond to stimuli that normally activate the gut.

The children in the study who received electrical stimulation were part of a larger group of 155 children with idiopathic, chronic, treatment-resistant constipation seen between 1995 and 2004. Children with known causes of chronic constipation, such as those with metabolic or genetic disorders, Hirschsprung's disease, or palpable fecalomas, were excluded from the study population. All of the subgroup had failed diet, laxative treatment, and behavioral therapy; the effects of constipation infringed upon school and play.

Transcutaneous stimulation using interferential current was applied for 20 minutes three times per week for 3–4 weeks using four surface electrodes, placed in front of and behind the umbilical area. Of the 16 children who received electrical stimulation, 81% showed increased defecation and 94% showed decreased soiling. The effects lasted for 3 months or more after stimulation. Dr. Southwell's work merited an Abstract of Distinction and Young Investigator Travel Award.

“Transcutaneous electrical stimulation was originally developed for bladder disorders. It has been used for more than 20 years so we know it is safe,” Dr. Southwell said in an interview. “We hope stimulation [for constipation] will develop into a technique that can be done in the home. Then it could be used by children anywhere, and also by the elderly. At the moment, it is a technique that must be done by physiotherapists.” Dr. Southwell leads a group in Gut Motility Research at the Murdoch Children's Research Institute, Royal Children's Hospital in Victoria (Australia).

The investigators used 48-hour radioisotope transit studies to follow movement through the colon and document STC. Of 155 studies, 20% showed normal transit, 20% anal retention, and 60% pancolonic slowing. (See these patterns in the illustration.)

Those with normal transit show accumulation in the cecum by 6 hours, radioactivity in the rectum by 30 hours, and no radioactivity by 48 hours because of elimination. Those with anal retention show radioactivity remaining in the rectum for 24–48 hours, whereas children with STC show radioactivity in the transverse or descending colons for 30–48 hours, at which point the rectum is still unreactive.

The researchers also evaluated neuromuscular function in children with STC by using 24-hour colonic manometry, in which a catheter with multiple recording sites spanning the colon is inserted via an appendix stoma to monitor contractions. When the results of 18 children with STC were compared with 8 non-STC children, those with STC had fewer anterior propagating contractions and showed no increase in gut activity upon awakening or after eating—findings consistent with poor contractions in the colon and slow transit constipation.

In another poster at the same meeting, Dr. Southwell's group at the Royal Children's Hospital in Victoria described findings suggesting that innervation of the gut wall may be compromised in STC. They reported lower levels of substance P and vasoactive intestinal peptide in biopsies taken from the right colon of children with STC, compared with constipated children without colonic dysmotility.

'We hope stimulation [for constipation] will develop into a technique that can be done in the home.' DR. SOUTHWELL

In 155 children, scintigraphy studies showed that about 20% had normal transit, 20% had anorectal retention, and 60% had slow colonic transit. Courtesy Dr. Bridget Southwell

MONTREAL — Characteristic changes on brain MRI can help diagnose and differentiate congenital muscular dystrophies with brain and eye abnormalities, reported Dr. Jiri Vajsar at the 10th International Child Neurology Congress.

Congenital muscular dystrophies (CMDs) with brain involvement share several common features, explained Dr. Vajsar, a neurologist affiliated with the Hospital for Sick Children in Toronto. All are autosomal recessive diseases that are characterized by early-onset hypotonia and weakness, delayed motor development, and elevated creatine kinase levels. Some CMD types also manifest mental retardation, delayed global development with subsequent regression, progressive contractures, seizures, variable ophthalmic findings, and cardiac and respiratory involvement.

Immunohistochemically, CMDs with brain involvement can be grouped into those with a deficiency in laminin-α2 chain (also known as merosin) or in α-dystroglycan, said Dr. Vajsar.

Both laminin-α2 chain and α-dystroglycan are part of a large complex of proteins and glycoproteins that protect the integrity of muscle cell structure during repeated cycles of contraction and relaxation. Poorly glycosylated α-dystroglycan corrupts laminin binding, weakening the link of muscle fibers to the extracellular matrix, and laminin-α2 chain deficiency results in disruption of the basal lamina of striated muscle.

MRIs of children with laminin-α2 chain deficiency show easily identifiable abnormalities in myelinated areas, although the corpus callosum and optic radiation remain normal. Despite the white matter abnormalities, these children maintain good cognitive function; however, about 30% are prone to seizures.

It is more difficult to generalize about the appearance on MRI of α-dystroglycan deficient CMDs, because several CMD phenotypes exist, said Dr. Vajsar. As a general rule, MRIs of these disorders show abnormalities in the posterior fossa, such as flattening of the pons, cerebellar hypoplasia or dysplasia, cerebellar cysts, and hypoplastic or absent vermis. The cortex takes on a cobblestone appearance, with disorganized cortical layers due to abnormal neuronal migration; multiple, abnormal, and coarse gyri with agyric regions; and variable thickness.

In Walker-Warburg syndrome (WWS), MRI findings include type II lissencephaly (cortical smoothing) and cerebellar malformation. Ventriculomegaly and abnormalities of corpus callosum and splenium are also common. Anterior (e.g., cataracts, microcornea, microphthalmia, lens defects) or posterior (e.g., retinal detachment, optic nerve atrophy, glaucoma) eye abnormalities are also frequent. Clinically, children with WWS are profoundly retarded, have seizures, and usually succumb to death within the first 3 years of life.

MRI findings in children with other CMD types show a spectrum of generally milder gray and white matter abnormalities, said Dr. Vajsar.

In muscle-eye-brain (MEB) disease, cortical, cerebellar, and callosum/splenium abnormalities are less prominent than in WWS. Polymicrogyria and thickened cortex may be noted in the frontal and parietal cortices, while agyria, cortical thinning, and lissencephaly may be evident in the occipital cortex.

MRI in patients with MDC type 1C may show normal brain with or without cerebellar cysts, said Dr. Vajsar. Occasionally, MRI shows other white and gray matter abnormalities, from cortical migrational anomalies and white matter changes to MEB-type or WWS patterns of abnormalities.

T2 image shows abnormal high signal in white matter (left) in CMD. Smooth cortex lacks sulcation; abnormalities of the corpus callosum and cerebellum and enlarged ventricles are consistent with WWS (middle). Thick cortex is indicative of MEB migrational abnormality (right). Photos courtesy Dr. Jiri Vajsar

MONTREAL — Characteristic changes on brain MRI can help diagnose and differentiate congenital muscular dystrophies with brain and eye abnormalities, reported Dr. Jiri Vajsar at the 10th International Child Neurology Congress.

Congenital muscular dystrophies (CMDs) with brain involvement share several common features, explained Dr. Vajsar, a neurologist affiliated with the Hospital for Sick Children in Toronto. All are autosomal recessive diseases that are characterized by early-onset hypotonia and weakness, delayed motor development, and elevated creatine kinase levels. Some CMD types also manifest mental retardation, delayed global development with subsequent regression, progressive contractures, seizures, variable ophthalmic findings, and cardiac and respiratory involvement.

Immunohistochemically, CMDs with brain involvement can be grouped into those with a deficiency in laminin-α2 chain (also known as merosin) or in α-dystroglycan, said Dr. Vajsar.

Both laminin-α2 chain and α-dystroglycan are part of a large complex of proteins and glycoproteins that protect the integrity of muscle cell structure during repeated cycles of contraction and relaxation. Poorly glycosylated α-dystroglycan corrupts laminin binding, weakening the link of muscle fibers to the extracellular matrix, and laminin-α2 chain deficiency results in disruption of the basal lamina of striated muscle.

MRIs of children with laminin-α2 chain deficiency show easily identifiable abnormalities in myelinated areas, although the corpus callosum and optic radiation remain normal. Despite the white matter abnormalities, these children maintain good cognitive function; however, about 30% are prone to seizures.

It is more difficult to generalize about the appearance on MRI of α-dystroglycan deficient CMDs, because several CMD phenotypes exist, said Dr. Vajsar. As a general rule, MRIs of these disorders show abnormalities in the posterior fossa, such as flattening of the pons, cerebellar hypoplasia or dysplasia, cerebellar cysts, and hypoplastic or absent vermis. The cortex takes on a cobblestone appearance, with disorganized cortical layers due to abnormal neuronal migration; multiple, abnormal, and coarse gyri with agyric regions; and variable thickness.

In Walker-Warburg syndrome (WWS), MRI findings include type II lissencephaly (cortical smoothing) and cerebellar malformation. Ventriculomegaly and abnormalities of corpus callosum and splenium are also common. Anterior (e.g., cataracts, microcornea, microphthalmia, lens defects) or posterior (e.g., retinal detachment, optic nerve atrophy, glaucoma) eye abnormalities are also frequent. Clinically, children with WWS are profoundly retarded, have seizures, and usually succumb to death within the first 3 years of life.

MRI findings in children with other CMD types show a spectrum of generally milder gray and white matter abnormalities, said Dr. Vajsar.

In muscle-eye-brain (MEB) disease, cortical, cerebellar, and callosum/splenium abnormalities are less prominent than in WWS. Polymicrogyria and thickened cortex may be noted in the frontal and parietal cortices, while agyria, cortical thinning, and lissencephaly may be evident in the occipital cortex.

MRI in patients with MDC type 1C may show normal brain with or without cerebellar cysts, said Dr. Vajsar. Occasionally, MRI shows other white and gray matter abnormalities, from cortical migrational anomalies and white matter changes to MEB-type or WWS patterns of abnormalities.

T2 image shows abnormal high signal in white matter (left) in CMD. Smooth cortex lacks sulcation; abnormalities of the corpus callosum and cerebellum and enlarged ventricles are consistent with WWS (middle). Thick cortex is indicative of MEB migrational abnormality (right). Photos courtesy Dr. Jiri Vajsar

MONTREAL — Characteristic changes on brain MRI can help diagnose and differentiate congenital muscular dystrophies with brain and eye abnormalities, reported Dr. Jiri Vajsar at the 10th International Child Neurology Congress.

Congenital muscular dystrophies (CMDs) with brain involvement share several common features, explained Dr. Vajsar, a neurologist affiliated with the Hospital for Sick Children in Toronto. All are autosomal recessive diseases that are characterized by early-onset hypotonia and weakness, delayed motor development, and elevated creatine kinase levels. Some CMD types also manifest mental retardation, delayed global development with subsequent regression, progressive contractures, seizures, variable ophthalmic findings, and cardiac and respiratory involvement.

Immunohistochemically, CMDs with brain involvement can be grouped into those with a deficiency in laminin-α2 chain (also known as merosin) or in α-dystroglycan, said Dr. Vajsar.

Both laminin-α2 chain and α-dystroglycan are part of a large complex of proteins and glycoproteins that protect the integrity of muscle cell structure during repeated cycles of contraction and relaxation. Poorly glycosylated α-dystroglycan corrupts laminin binding, weakening the link of muscle fibers to the extracellular matrix, and laminin-α2 chain deficiency results in disruption of the basal lamina of striated muscle.

MRIs of children with laminin-α2 chain deficiency show easily identifiable abnormalities in myelinated areas, although the corpus callosum and optic radiation remain normal. Despite the white matter abnormalities, these children maintain good cognitive function; however, about 30% are prone to seizures.

It is more difficult to generalize about the appearance on MRI of α-dystroglycan deficient CMDs, because several CMD phenotypes exist, said Dr. Vajsar. As a general rule, MRIs of these disorders show abnormalities in the posterior fossa, such as flattening of the pons, cerebellar hypoplasia or dysplasia, cerebellar cysts, and hypoplastic or absent vermis. The cortex takes on a cobblestone appearance, with disorganized cortical layers due to abnormal neuronal migration; multiple, abnormal, and coarse gyri with agyric regions; and variable thickness.

In Walker-Warburg syndrome (WWS), MRI findings include type II lissencephaly (cortical smoothing) and cerebellar malformation. Ventriculomegaly and abnormalities of corpus callosum and splenium are also common. Anterior (e.g., cataracts, microcornea, microphthalmia, lens defects) or posterior (e.g., retinal detachment, optic nerve atrophy, glaucoma) eye abnormalities are also frequent. Clinically, children with WWS are profoundly retarded, have seizures, and usually succumb to death within the first 3 years of life.

MRI findings in children with other CMD types show a spectrum of generally milder gray and white matter abnormalities, said Dr. Vajsar.

In muscle-eye-brain (MEB) disease, cortical, cerebellar, and callosum/splenium abnormalities are less prominent than in WWS. Polymicrogyria and thickened cortex may be noted in the frontal and parietal cortices, while agyria, cortical thinning, and lissencephaly may be evident in the occipital cortex.

MRI in patients with MDC type 1C may show normal brain with or without cerebellar cysts, said Dr. Vajsar. Occasionally, MRI shows other white and gray matter abnormalities, from cortical migrational anomalies and white matter changes to MEB-type or WWS patterns of abnormalities.

T2 image shows abnormal high signal in white matter (left) in CMD. Smooth cortex lacks sulcation; abnormalities of the corpus callosum and cerebellum and enlarged ventricles are consistent with WWS (middle). Thick cortex is indicative of MEB migrational abnormality (right). Photos courtesy Dr. Jiri Vajsar

MONTREAL – Volumetric measurement of the brains of children with learning disabilities of unknown etiology has revealed subtle abnormalities in regions associated with the anterior thalamocortical tract that correlate with the severity of the learning disability, according to a report that merited the Best Abstract Award in a Clinical Topic at the 10th International Child Neurology Congress.

This Finnish study examined 122 children (average age, 12 years) who had learning problems that ranged from mild specific disabilities to severe intellectual limitations. A group of 43 children in mainstream education served as controls, said Dr. Taina Autti, who is with the Helsinki Medical Imaging Center and Helsinki University Central Hospital.

The children underwent conventional magnetic resonance imaging with a 1.5-tesla magnet.

Three-dimensional images were then generated for volumetric analyses, and fluid-attenuated inversion recovery (FLAIR) and T2-weighted coronal images were examined for possible abnormalities. Voxel-based morphometry was used to compare local volumes of gray matter, white matter, and cerebrospinal fluid between study groups. Each voxel was 1 mm

Thirteen children were found to have structural abnormalities, such as optic glioma, enlarged ventricles, enlarged sulci, and vermis atrophy, and were eliminated from further analysis. For the remaining 152 participants, conventional MRI showed no apparent gross structural abnormalities.

When the investigators searched for brain areas where local volume correlated with degree of learning disability, several regions stood out:

▸ In the anterior cingulate cortex, a significant positive correlation was found with gray matter volume (Tmax = 5.50, P < .001). (See images.)

▸ In the left frontoparietal lobe, a significant positive correlation was found with white matter volume (Tmax = 5.34, P < .001).

▸ In the left thalamus, a significant negative correlation was found with gray matter volume (Tmax = 5.26, P < .001).

▸ In the posterior internal capsules, a significant negative correlation was found with white matter volume (TmaxRight = 5.57, P < .001; TmaxLeft = 5.20, P < .001).

The study findings indicate dysfunction of the anterior thalamocortical tracts, which begin in the anterior mediodorsal nucleus of the thalamus, pass through the anterior internal capsule, and terminate in the anterior cingulate gyrus or prefrontal cortex, according to Dr. Autti.

The anterior cingulate cortex plays a central role in many cognitive tasks–functions that are often disturbed in children with learning disabilities, Dr. Autti said. These include cognitive flexibility, initiation of appropriate behaviors, suppression of inappropriate behaviors, attentiveness, adaptability, alertness, motivation, fluid thought transfer, and the ability to evaluate options and make choices. “The greater gray volume in the anterior cingulate cortex may be the unifying feature in learning disabilities of unexplained, familial etiology,” Dr. Autti said.

MONTREAL – Volumetric measurement of the brains of children with learning disabilities of unknown etiology has revealed subtle abnormalities in regions associated with the anterior thalamocortical tract that correlate with the severity of the learning disability, according to a report that merited the Best Abstract Award in a Clinical Topic at the 10th International Child Neurology Congress.

This Finnish study examined 122 children (average age, 12 years) who had learning problems that ranged from mild specific disabilities to severe intellectual limitations. A group of 43 children in mainstream education served as controls, said Dr. Taina Autti, who is with the Helsinki Medical Imaging Center and Helsinki University Central Hospital.

The children underwent conventional magnetic resonance imaging with a 1.5-tesla magnet.

Three-dimensional images were then generated for volumetric analyses, and fluid-attenuated inversion recovery (FLAIR) and T2-weighted coronal images were examined for possible abnormalities. Voxel-based morphometry was used to compare local volumes of gray matter, white matter, and cerebrospinal fluid between study groups. Each voxel was 1 mm

Thirteen children were found to have structural abnormalities, such as optic glioma, enlarged ventricles, enlarged sulci, and vermis atrophy, and were eliminated from further analysis. For the remaining 152 participants, conventional MRI showed no apparent gross structural abnormalities.

When the investigators searched for brain areas where local volume correlated with degree of learning disability, several regions stood out:

▸ In the anterior cingulate cortex, a significant positive correlation was found with gray matter volume (Tmax = 5.50, P < .001). (See images.)

▸ In the left frontoparietal lobe, a significant positive correlation was found with white matter volume (Tmax = 5.34, P < .001).

▸ In the left thalamus, a significant negative correlation was found with gray matter volume (Tmax = 5.26, P < .001).

▸ In the posterior internal capsules, a significant negative correlation was found with white matter volume (TmaxRight = 5.57, P < .001; TmaxLeft = 5.20, P < .001).

The study findings indicate dysfunction of the anterior thalamocortical tracts, which begin in the anterior mediodorsal nucleus of the thalamus, pass through the anterior internal capsule, and terminate in the anterior cingulate gyrus or prefrontal cortex, according to Dr. Autti.

The anterior cingulate cortex plays a central role in many cognitive tasks–functions that are often disturbed in children with learning disabilities, Dr. Autti said. These include cognitive flexibility, initiation of appropriate behaviors, suppression of inappropriate behaviors, attentiveness, adaptability, alertness, motivation, fluid thought transfer, and the ability to evaluate options and make choices. “The greater gray volume in the anterior cingulate cortex may be the unifying feature in learning disabilities of unexplained, familial etiology,” Dr. Autti said.

MONTREAL – Volumetric measurement of the brains of children with learning disabilities of unknown etiology has revealed subtle abnormalities in regions associated with the anterior thalamocortical tract that correlate with the severity of the learning disability, according to a report that merited the Best Abstract Award in a Clinical Topic at the 10th International Child Neurology Congress.

This Finnish study examined 122 children (average age, 12 years) who had learning problems that ranged from mild specific disabilities to severe intellectual limitations. A group of 43 children in mainstream education served as controls, said Dr. Taina Autti, who is with the Helsinki Medical Imaging Center and Helsinki University Central Hospital.

The children underwent conventional magnetic resonance imaging with a 1.5-tesla magnet.

Three-dimensional images were then generated for volumetric analyses, and fluid-attenuated inversion recovery (FLAIR) and T2-weighted coronal images were examined for possible abnormalities. Voxel-based morphometry was used to compare local volumes of gray matter, white matter, and cerebrospinal fluid between study groups. Each voxel was 1 mm

Thirteen children were found to have structural abnormalities, such as optic glioma, enlarged ventricles, enlarged sulci, and vermis atrophy, and were eliminated from further analysis. For the remaining 152 participants, conventional MRI showed no apparent gross structural abnormalities.

When the investigators searched for brain areas where local volume correlated with degree of learning disability, several regions stood out:

▸ In the anterior cingulate cortex, a significant positive correlation was found with gray matter volume (Tmax = 5.50, P < .001). (See images.)

▸ In the left frontoparietal lobe, a significant positive correlation was found with white matter volume (Tmax = 5.34, P < .001).

▸ In the left thalamus, a significant negative correlation was found with gray matter volume (Tmax = 5.26, P < .001).

▸ In the posterior internal capsules, a significant negative correlation was found with white matter volume (TmaxRight = 5.57, P < .001; TmaxLeft = 5.20, P < .001).

The study findings indicate dysfunction of the anterior thalamocortical tracts, which begin in the anterior mediodorsal nucleus of the thalamus, pass through the anterior internal capsule, and terminate in the anterior cingulate gyrus or prefrontal cortex, according to Dr. Autti.

The anterior cingulate cortex plays a central role in many cognitive tasks–functions that are often disturbed in children with learning disabilities, Dr. Autti said. These include cognitive flexibility, initiation of appropriate behaviors, suppression of inappropriate behaviors, attentiveness, adaptability, alertness, motivation, fluid thought transfer, and the ability to evaluate options and make choices. “The greater gray volume in the anterior cingulate cortex may be the unifying feature in learning disabilities of unexplained, familial etiology,” Dr. Autti said.

SAN DIEGO – Positron emission tomography/computed tomography can reveal seizure foci in patients with temporal lobe epilepsy who have normal magnetic resonance imaging.

PET/CT is more sensitive than ictal single-photon emission computed tomography (SPECT) imaging, MRI diffusion imaging (MRI-DI), and electroencephalography, and can play a pivotal role in the preoperative imaging work-up of patients with temporal lobe epilepsy, Dr. Jay J. Pillai reported at the annual meeting of the American Society of Neuroradiology.

In this retrospective study, 21 patients with EEG and clinical evidence of temporal lobe epilepsy underwent interictal PET/CT and structural MRI (1.5 Tesla), and 19 also underwent interictal MRI-DI. Ictal SPECT imaging was performed on six of these patients. Dr. Pillai stressed that these findings were only preliminary, and that additional investigation will be necessary to confirm these initial findings with a larger patient sample.

Eight patients had no structural abnormality on MRI. In all of these cases, PET/CT was able to lateralize the seizure focus. EEG was helpful in one case, and abnormal diffusion in the temporal lobes was detected with MRI-DI in two cases.

In the group overall, PET/CT was able to establish seizure focus lateralization in 95% of cases, a rate almost twice as high as that reported with structural MRI (52%), said Dr. Pillai, director of neuro-MRI at the Medical College of Georgia, Augusta. The sensitivity of PET/CT was higher than that found for ictal SPECT (83%), EEG (62%), and MRI-DI (58%).

Looking at how often the PET/CT and EEG findings concurred regarding the location of the seizure focus, Dr. Pillai found that PET/CT and EEG findings were in agreement 88% of the time, while lower rates of concordance were found for MRI-DI (59%) and ictal SPECT (60%). With MRI-DI, apparent diffusion coefficient (ADC) values in the abnormal temporal lobe were significantly higher than those in the normal contralateral temporal lobe. These ADC values are measures of magnitude of water diffusion in the brain.

In his presentation, Dr. Pillai described two patients in whom the various imaging modalities revealed discordant or otherwise inconclusive results. In these instances, PET/CT demonstrated definitive lateralization of the seizure focus, which the combination of interictal EEG, structural MRI, MRI-DI, and ictal SPECT failed to show to any convincing degree.

The results suggest that PET/CT may prove to be a highly sensitive method of localizing seizure foci in the temporal lobe, especially when findings from EEG and other imaging modalities are contradictory or falsely negative.

PET/CT findings were in accord with EEGs more often than were other imaging modalities. DR. PILLAI

SAN DIEGO – Positron emission tomography/computed tomography can reveal seizure foci in patients with temporal lobe epilepsy who have normal magnetic resonance imaging.

PET/CT is more sensitive than ictal single-photon emission computed tomography (SPECT) imaging, MRI diffusion imaging (MRI-DI), and electroencephalography, and can play a pivotal role in the preoperative imaging work-up of patients with temporal lobe epilepsy, Dr. Jay J. Pillai reported at the annual meeting of the American Society of Neuroradiology.

In this retrospective study, 21 patients with EEG and clinical evidence of temporal lobe epilepsy underwent interictal PET/CT and structural MRI (1.5 Tesla), and 19 also underwent interictal MRI-DI. Ictal SPECT imaging was performed on six of these patients. Dr. Pillai stressed that these findings were only preliminary, and that additional investigation will be necessary to confirm these initial findings with a larger patient sample.

Eight patients had no structural abnormality on MRI. In all of these cases, PET/CT was able to lateralize the seizure focus. EEG was helpful in one case, and abnormal diffusion in the temporal lobes was detected with MRI-DI in two cases.

In the group overall, PET/CT was able to establish seizure focus lateralization in 95% of cases, a rate almost twice as high as that reported with structural MRI (52%), said Dr. Pillai, director of neuro-MRI at the Medical College of Georgia, Augusta. The sensitivity of PET/CT was higher than that found for ictal SPECT (83%), EEG (62%), and MRI-DI (58%).

Looking at how often the PET/CT and EEG findings concurred regarding the location of the seizure focus, Dr. Pillai found that PET/CT and EEG findings were in agreement 88% of the time, while lower rates of concordance were found for MRI-DI (59%) and ictal SPECT (60%). With MRI-DI, apparent diffusion coefficient (ADC) values in the abnormal temporal lobe were significantly higher than those in the normal contralateral temporal lobe. These ADC values are measures of magnitude of water diffusion in the brain.

In his presentation, Dr. Pillai described two patients in whom the various imaging modalities revealed discordant or otherwise inconclusive results. In these instances, PET/CT demonstrated definitive lateralization of the seizure focus, which the combination of interictal EEG, structural MRI, MRI-DI, and ictal SPECT failed to show to any convincing degree.

The results suggest that PET/CT may prove to be a highly sensitive method of localizing seizure foci in the temporal lobe, especially when findings from EEG and other imaging modalities are contradictory or falsely negative.

PET/CT findings were in accord with EEGs more often than were other imaging modalities. DR. PILLAI

SAN DIEGO – Positron emission tomography/computed tomography can reveal seizure foci in patients with temporal lobe epilepsy who have normal magnetic resonance imaging.

PET/CT is more sensitive than ictal single-photon emission computed tomography (SPECT) imaging, MRI diffusion imaging (MRI-DI), and electroencephalography, and can play a pivotal role in the preoperative imaging work-up of patients with temporal lobe epilepsy, Dr. Jay J. Pillai reported at the annual meeting of the American Society of Neuroradiology.

In this retrospective study, 21 patients with EEG and clinical evidence of temporal lobe epilepsy underwent interictal PET/CT and structural MRI (1.5 Tesla), and 19 also underwent interictal MRI-DI. Ictal SPECT imaging was performed on six of these patients. Dr. Pillai stressed that these findings were only preliminary, and that additional investigation will be necessary to confirm these initial findings with a larger patient sample.

Eight patients had no structural abnormality on MRI. In all of these cases, PET/CT was able to lateralize the seizure focus. EEG was helpful in one case, and abnormal diffusion in the temporal lobes was detected with MRI-DI in two cases.

In the group overall, PET/CT was able to establish seizure focus lateralization in 95% of cases, a rate almost twice as high as that reported with structural MRI (52%), said Dr. Pillai, director of neuro-MRI at the Medical College of Georgia, Augusta. The sensitivity of PET/CT was higher than that found for ictal SPECT (83%), EEG (62%), and MRI-DI (58%).

Looking at how often the PET/CT and EEG findings concurred regarding the location of the seizure focus, Dr. Pillai found that PET/CT and EEG findings were in agreement 88% of the time, while lower rates of concordance were found for MRI-DI (59%) and ictal SPECT (60%). With MRI-DI, apparent diffusion coefficient (ADC) values in the abnormal temporal lobe were significantly higher than those in the normal contralateral temporal lobe. These ADC values are measures of magnitude of water diffusion in the brain.

In his presentation, Dr. Pillai described two patients in whom the various imaging modalities revealed discordant or otherwise inconclusive results. In these instances, PET/CT demonstrated definitive lateralization of the seizure focus, which the combination of interictal EEG, structural MRI, MRI-DI, and ictal SPECT failed to show to any convincing degree.

The results suggest that PET/CT may prove to be a highly sensitive method of localizing seizure foci in the temporal lobe, especially when findings from EEG and other imaging modalities are contradictory or falsely negative.

PET/CT findings were in accord with EEGs more often than were other imaging modalities. DR. PILLAI

MONTREAL — Ibuprofen significantly alleviated children's headache symptoms compared with placebo, according to findings from a metaanalysis of randomized controlled trials that focused on drug therapy for pediatric migraines, Dr. Lori L. Billinghurst said at the 10th International Child Neurology Congress.

Of more than 4,000 possible inclusions identified from six electronic bibliographic databases, 14 studies met all inclusion criteria. Two randomized controlled trials (RCTs) demonstrated that ibuprofen significantly alleviated headache symptoms, provided complete headache relief, and prevented headache recurrence compared to placebo; no benefits, however, were found for acetaminophen or dihydroergotamine compared to placebo. In one RCT, the dopamine antagonist prochlorperazine was more effective than the NSAID ketorolac, said Dr. Billinghurst, a neurology resident at the University of Alberta, Edmonton.

As a group, the triptans were better than placebo for alleviating headaches (RR 1.13; 95% CI 1.06, 1.20) and providing complete headache relief (RR 1.34; 95% CI 1.18, 1.52), with sumatriptan the only effective individual medication of the class. Rizatriptan improved headache relief compared with standard care.

The metaanalysis also showed a very high placebo rate of 47% for headache alleviation and 21% for headache relief, said Dr. Billinghurst. Because this problem has become a major impediment for clinical trials, new and innovative study designs are needed to evaluate the efficacy of therapies.

Taken together, these reports reveal disconnection between evidence and practice for acute treatment of pediatric migraines. For instance, there is no evidence to support the use of opiates—but opiates are offered, especially in adult emergency departments. On the other hand, there is evidence to support the use of triptans, especially intranasal sumatriptan, for acute migraine relief—but these were not options in either the adult or pediatric emergency department setting. The evidence also suggests that ibuprofen is a better choice than acetaminophen for pediatric migraine. The high placebo rate noted in RCTs suggested that no treatment or just supportive treatment (e.g., intravenous fluids) may sometimes be an appropriate path to follow.

The results also underscore the need for practice management guidelines to ensure consistency of diagnosis and treatment of pediatric migraines in the acute setting, as well as to highlight the need for more RCTs to assess the safety, tolerability, and efficacy of medications such as dopamine antagonists for migraines in children.

MONTREAL — Ibuprofen significantly alleviated children's headache symptoms compared with placebo, according to findings from a metaanalysis of randomized controlled trials that focused on drug therapy for pediatric migraines, Dr. Lori L. Billinghurst said at the 10th International Child Neurology Congress.

Of more than 4,000 possible inclusions identified from six electronic bibliographic databases, 14 studies met all inclusion criteria. Two randomized controlled trials (RCTs) demonstrated that ibuprofen significantly alleviated headache symptoms, provided complete headache relief, and prevented headache recurrence compared to placebo; no benefits, however, were found for acetaminophen or dihydroergotamine compared to placebo. In one RCT, the dopamine antagonist prochlorperazine was more effective than the NSAID ketorolac, said Dr. Billinghurst, a neurology resident at the University of Alberta, Edmonton.

As a group, the triptans were better than placebo for alleviating headaches (RR 1.13; 95% CI 1.06, 1.20) and providing complete headache relief (RR 1.34; 95% CI 1.18, 1.52), with sumatriptan the only effective individual medication of the class. Rizatriptan improved headache relief compared with standard care.

The metaanalysis also showed a very high placebo rate of 47% for headache alleviation and 21% for headache relief, said Dr. Billinghurst. Because this problem has become a major impediment for clinical trials, new and innovative study designs are needed to evaluate the efficacy of therapies.

Taken together, these reports reveal disconnection between evidence and practice for acute treatment of pediatric migraines. For instance, there is no evidence to support the use of opiates—but opiates are offered, especially in adult emergency departments. On the other hand, there is evidence to support the use of triptans, especially intranasal sumatriptan, for acute migraine relief—but these were not options in either the adult or pediatric emergency department setting. The evidence also suggests that ibuprofen is a better choice than acetaminophen for pediatric migraine. The high placebo rate noted in RCTs suggested that no treatment or just supportive treatment (e.g., intravenous fluids) may sometimes be an appropriate path to follow.

The results also underscore the need for practice management guidelines to ensure consistency of diagnosis and treatment of pediatric migraines in the acute setting, as well as to highlight the need for more RCTs to assess the safety, tolerability, and efficacy of medications such as dopamine antagonists for migraines in children.

MONTREAL — Ibuprofen significantly alleviated children's headache symptoms compared with placebo, according to findings from a metaanalysis of randomized controlled trials that focused on drug therapy for pediatric migraines, Dr. Lori L. Billinghurst said at the 10th International Child Neurology Congress.

Of more than 4,000 possible inclusions identified from six electronic bibliographic databases, 14 studies met all inclusion criteria. Two randomized controlled trials (RCTs) demonstrated that ibuprofen significantly alleviated headache symptoms, provided complete headache relief, and prevented headache recurrence compared to placebo; no benefits, however, were found for acetaminophen or dihydroergotamine compared to placebo. In one RCT, the dopamine antagonist prochlorperazine was more effective than the NSAID ketorolac, said Dr. Billinghurst, a neurology resident at the University of Alberta, Edmonton.

As a group, the triptans were better than placebo for alleviating headaches (RR 1.13; 95% CI 1.06, 1.20) and providing complete headache relief (RR 1.34; 95% CI 1.18, 1.52), with sumatriptan the only effective individual medication of the class. Rizatriptan improved headache relief compared with standard care.

The metaanalysis also showed a very high placebo rate of 47% for headache alleviation and 21% for headache relief, said Dr. Billinghurst. Because this problem has become a major impediment for clinical trials, new and innovative study designs are needed to evaluate the efficacy of therapies.

Taken together, these reports reveal disconnection between evidence and practice for acute treatment of pediatric migraines. For instance, there is no evidence to support the use of opiates—but opiates are offered, especially in adult emergency departments. On the other hand, there is evidence to support the use of triptans, especially intranasal sumatriptan, for acute migraine relief—but these were not options in either the adult or pediatric emergency department setting. The evidence also suggests that ibuprofen is a better choice than acetaminophen for pediatric migraine. The high placebo rate noted in RCTs suggested that no treatment or just supportive treatment (e.g., intravenous fluids) may sometimes be an appropriate path to follow.

The results also underscore the need for practice management guidelines to ensure consistency of diagnosis and treatment of pediatric migraines in the acute setting, as well as to highlight the need for more RCTs to assess the safety, tolerability, and efficacy of medications such as dopamine antagonists for migraines in children.

MONTREAL — Children with acute migraine are less likely to be treated according to practice guidelines or with a medication of proven efficacy for pediatric populations, or to have been effectively treated at all if they are cared for in an adult rather than pediatric emergency department, according to a presentation by Dr. Lawrence Richer at the 10th International Child Neurology Congress.

“Adult and pediatric ERs within the same city differ in their treatment of headaches and migraines in children,” commented Dr. Richer, a pediatric neurologist at the University of Alberta, Edmonton, who said this choice “remains the single most important factor in determining outcome.”

Investigators conducted a chart review of 382 children treated for headache or migraine between July 2003 and July 2004 in four emergency departments (three adult, one pediatric) in Edmonton. Of these children, 65% were seen in the pediatric emergency department. The children ranged in age from 2 to 17 years, with a mean age of 11.4 years. About 12% had a previous head injury, and about 11% had symptoms of recent infection.

Richer found management differed between adult and pediatric emergency departments. Children with acute migraines were more likely to have blood work, a lumbar puncture, or a computed tomography scan or other neuroimaging procedure if they were treated at an adult ED than if they went to the pediatric ED.

Children in adult EDs were less likely to be given more than one treatment and more likely to be discharged while symptoms remained unresolved.

NSAIDs—most often acetaminophen—were the most popular first-line therapies in both EDs. Opiates such as codeine and morphine were used less often, although when given they were administered more frequently for children seen in adult EDs than pediatric EDs. Dopamine antagonists were more often prescribed in pediatric than adult EDs. Oral or intravenous triptans were not used in the emergency setting.

Do these treatment choices reflect practice guidelines? In December 2004 (midway through the patient acquisition phase of Dr. Richer's study), the American Academy of Neurology released guidelines for treating patients with pediatric migraine, and these guidelines were endorsed by the American Academy of Pediatrics and the American Headache Society (Neurology 2004;63:2215–24).

Although no agents are currently approved by the Food and Drug Administration for the acute treatment of migraine in children or adolescents, the guidelines indicated evidence that ibuprofen was effective and acetaminophen was probably effective. No mention was made of the use of opioids. While the guidelines indicated that no adequate data supported or refuted the use of any oral or subcutaneous triptan preparation, good data were available favoring the use of sumatriptan nasal spray for adolescents—a medication apparently not offered by the emergency departments surveyed.

MONTREAL — Children with acute migraine are less likely to be treated according to practice guidelines or with a medication of proven efficacy for pediatric populations, or to have been effectively treated at all if they are cared for in an adult rather than pediatric emergency department, according to a presentation by Dr. Lawrence Richer at the 10th International Child Neurology Congress.

“Adult and pediatric ERs within the same city differ in their treatment of headaches and migraines in children,” commented Dr. Richer, a pediatric neurologist at the University of Alberta, Edmonton, who said this choice “remains the single most important factor in determining outcome.”

Investigators conducted a chart review of 382 children treated for headache or migraine between July 2003 and July 2004 in four emergency departments (three adult, one pediatric) in Edmonton. Of these children, 65% were seen in the pediatric emergency department. The children ranged in age from 2 to 17 years, with a mean age of 11.4 years. About 12% had a previous head injury, and about 11% had symptoms of recent infection.

Richer found management differed between adult and pediatric emergency departments. Children with acute migraines were more likely to have blood work, a lumbar puncture, or a computed tomography scan or other neuroimaging procedure if they were treated at an adult ED than if they went to the pediatric ED.

Children in adult EDs were less likely to be given more than one treatment and more likely to be discharged while symptoms remained unresolved.

NSAIDs—most often acetaminophen—were the most popular first-line therapies in both EDs. Opiates such as codeine and morphine were used less often, although when given they were administered more frequently for children seen in adult EDs than pediatric EDs. Dopamine antagonists were more often prescribed in pediatric than adult EDs. Oral or intravenous triptans were not used in the emergency setting.

Do these treatment choices reflect practice guidelines? In December 2004 (midway through the patient acquisition phase of Dr. Richer's study), the American Academy of Neurology released guidelines for treating patients with pediatric migraine, and these guidelines were endorsed by the American Academy of Pediatrics and the American Headache Society (Neurology 2004;63:2215–24).

Although no agents are currently approved by the Food and Drug Administration for the acute treatment of migraine in children or adolescents, the guidelines indicated evidence that ibuprofen was effective and acetaminophen was probably effective. No mention was made of the use of opioids. While the guidelines indicated that no adequate data supported or refuted the use of any oral or subcutaneous triptan preparation, good data were available favoring the use of sumatriptan nasal spray for adolescents—a medication apparently not offered by the emergency departments surveyed.

MONTREAL — Children with acute migraine are less likely to be treated according to practice guidelines or with a medication of proven efficacy for pediatric populations, or to have been effectively treated at all if they are cared for in an adult rather than pediatric emergency department, according to a presentation by Dr. Lawrence Richer at the 10th International Child Neurology Congress.

“Adult and pediatric ERs within the same city differ in their treatment of headaches and migraines in children,” commented Dr. Richer, a pediatric neurologist at the University of Alberta, Edmonton, who said this choice “remains the single most important factor in determining outcome.”

Investigators conducted a chart review of 382 children treated for headache or migraine between July 2003 and July 2004 in four emergency departments (three adult, one pediatric) in Edmonton. Of these children, 65% were seen in the pediatric emergency department. The children ranged in age from 2 to 17 years, with a mean age of 11.4 years. About 12% had a previous head injury, and about 11% had symptoms of recent infection.

Richer found management differed between adult and pediatric emergency departments. Children with acute migraines were more likely to have blood work, a lumbar puncture, or a computed tomography scan or other neuroimaging procedure if they were treated at an adult ED than if they went to the pediatric ED.

Children in adult EDs were less likely to be given more than one treatment and more likely to be discharged while symptoms remained unresolved.

NSAIDs—most often acetaminophen—were the most popular first-line therapies in both EDs. Opiates such as codeine and morphine were used less often, although when given they were administered more frequently for children seen in adult EDs than pediatric EDs. Dopamine antagonists were more often prescribed in pediatric than adult EDs. Oral or intravenous triptans were not used in the emergency setting.

Do these treatment choices reflect practice guidelines? In December 2004 (midway through the patient acquisition phase of Dr. Richer's study), the American Academy of Neurology released guidelines for treating patients with pediatric migraine, and these guidelines were endorsed by the American Academy of Pediatrics and the American Headache Society (Neurology 2004;63:2215–24).

Although no agents are currently approved by the Food and Drug Administration for the acute treatment of migraine in children or adolescents, the guidelines indicated evidence that ibuprofen was effective and acetaminophen was probably effective. No mention was made of the use of opioids. While the guidelines indicated that no adequate data supported or refuted the use of any oral or subcutaneous triptan preparation, good data were available favoring the use of sumatriptan nasal spray for adolescents—a medication apparently not offered by the emergency departments surveyed.