Michele G. Sullivan

CAMBRIDGE, MD. — Gastric bypass surgery can improve liver pathology in patients who have been diagnosed with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, Dr. Kris V. Kowdley said at a hepatobiliary update sponsored by Johns Hopkins University.

Some researchers have expressed concerns that the dramatic and rapid weight loss associated with gastric bypass surgery could actually exacerbate nonalcoholic fatty liver disease (NAFLD), but that “clearly is not the case,” said Dr. Kowdley of the University of Washington, Seattle.

Two recent studies support the beneficial effect of gastroplasty on this spectrum of liver pathology. A 2004 study included 23 patients with nonalcoholic steatohepatitis (NASH) and 12 with simple steatosis. Liver biopsies were obtained from all patients about 2 years after surgery. There were major improvements in lobular steatosis, necroinflammatory changes, and fibrosis; only four patients still fulfilled the criteria for NASH. Improvements were most pronounced in those with metabolic syndrome (Hepatology 2004;39:1647–54).

A 2005 study examined the results of gastric bypass in 16 patients whose mean presurgery weight was 334 pounds. A follow-up liver biopsy was performed about 1 year later. Steatosis had improved in 15 patients, with resolution in 13. Of 15 patients who had inflammation at baseline, 12 showed improvement, and 12 of 14 showed less ballooning. Six of 14 patients with perisinusoidal fibrosis and 6 of 13 with portal fibrosis showed improvement. No patient had worsening of steatosis, inflammation, ballooning, or fibrosis (Obes. Res. 2005;13:1180–6).

NAFLD is part of a histopathologic spectrum of liver injury that ranges from simple steatosis to necroinflammatory changes that may progress to cirrhosis. NASH is associated with increased risk of hepatocellular cancer and liver-related death.

The etiology of these disorders is poorly understood but is thought to be a “two-hit” process beginning with fat accumulation in the liver, most often in the presence of obesity, insulin resistance, or type 2 diabetes. “The 'second hit' is presumed to be any number of processes that contribute to oxidative injury in the liver,” Dr. Kowdley said, and could include oxidative stress that interferes with mitochondrial function.

Most patients with NAFLD are asymptomatic; their disease is discovered when screening tests identify abnormal liver function. Many are obese; studies suggest that about 30% of patients who undergo gastric bypass have the disease. But the pattern of fat deposition is perhaps more important than the patient's weight, Dr. Kowdley said; NAFLD is highly associated with truncal obesity.

On ultrasound, the fatty liver typically appears diffusely hyperechoic in relation to the spleen and kidneys. Computed tomography and magnetic resonance imaging may show focal fat deposits. However, a liver biopsy is the most sensitive and specific means of diagnosis and can differentiate simple steatohepatitis from more advanced stages of the disease in which fibrosis may be present.

There are no approved pharmacologic therapies for NAFLD. Several drugs are under investigation, including metformin and thiazolidinediones.

“Weight loss is one highly recommended method of dealing with NAFLD,” Dr. Kowdley said. “Even a modest amount of weight loss, say 20 pounds, significantly decreases the fasting insulin level and improves liver enzymes, and those improvements are maintained as long as weight loss is maintained. A 40% reduction from initial alanine aminotransferase levels can be achieved.”

All patients with NAFLD should be counseled to lose weight through a combination of diet and exercise. Those with a body mass index (BMI) greater than 30 kg/m

CAMBRIDGE, MD. — Gastric bypass surgery can improve liver pathology in patients who have been diagnosed with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, Dr. Kris V. Kowdley said at a hepatobiliary update sponsored by Johns Hopkins University.

Some researchers have expressed concerns that the dramatic and rapid weight loss associated with gastric bypass surgery could actually exacerbate nonalcoholic fatty liver disease (NAFLD), but that “clearly is not the case,” said Dr. Kowdley of the University of Washington, Seattle.

Two recent studies support the beneficial effect of gastroplasty on this spectrum of liver pathology. A 2004 study included 23 patients with nonalcoholic steatohepatitis (NASH) and 12 with simple steatosis. Liver biopsies were obtained from all patients about 2 years after surgery. There were major improvements in lobular steatosis, necroinflammatory changes, and fibrosis; only four patients still fulfilled the criteria for NASH. Improvements were most pronounced in those with metabolic syndrome (Hepatology 2004;39:1647–54).

A 2005 study examined the results of gastric bypass in 16 patients whose mean presurgery weight was 334 pounds. A follow-up liver biopsy was performed about 1 year later. Steatosis had improved in 15 patients, with resolution in 13. Of 15 patients who had inflammation at baseline, 12 showed improvement, and 12 of 14 showed less ballooning. Six of 14 patients with perisinusoidal fibrosis and 6 of 13 with portal fibrosis showed improvement. No patient had worsening of steatosis, inflammation, ballooning, or fibrosis (Obes. Res. 2005;13:1180–6).

NAFLD is part of a histopathologic spectrum of liver injury that ranges from simple steatosis to necroinflammatory changes that may progress to cirrhosis. NASH is associated with increased risk of hepatocellular cancer and liver-related death.

The etiology of these disorders is poorly understood but is thought to be a “two-hit” process beginning with fat accumulation in the liver, most often in the presence of obesity, insulin resistance, or type 2 diabetes. “The 'second hit' is presumed to be any number of processes that contribute to oxidative injury in the liver,” Dr. Kowdley said, and could include oxidative stress that interferes with mitochondrial function.

Most patients with NAFLD are asymptomatic; their disease is discovered when screening tests identify abnormal liver function. Many are obese; studies suggest that about 30% of patients who undergo gastric bypass have the disease. But the pattern of fat deposition is perhaps more important than the patient's weight, Dr. Kowdley said; NAFLD is highly associated with truncal obesity.

On ultrasound, the fatty liver typically appears diffusely hyperechoic in relation to the spleen and kidneys. Computed tomography and magnetic resonance imaging may show focal fat deposits. However, a liver biopsy is the most sensitive and specific means of diagnosis and can differentiate simple steatohepatitis from more advanced stages of the disease in which fibrosis may be present.

There are no approved pharmacologic therapies for NAFLD. Several drugs are under investigation, including metformin and thiazolidinediones.

“Weight loss is one highly recommended method of dealing with NAFLD,” Dr. Kowdley said. “Even a modest amount of weight loss, say 20 pounds, significantly decreases the fasting insulin level and improves liver enzymes, and those improvements are maintained as long as weight loss is maintained. A 40% reduction from initial alanine aminotransferase levels can be achieved.”

All patients with NAFLD should be counseled to lose weight through a combination of diet and exercise. Those with a body mass index (BMI) greater than 30 kg/m

CAMBRIDGE, MD. — Gastric bypass surgery can improve liver pathology in patients who have been diagnosed with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, Dr. Kris V. Kowdley said at a hepatobiliary update sponsored by Johns Hopkins University.

Some researchers have expressed concerns that the dramatic and rapid weight loss associated with gastric bypass surgery could actually exacerbate nonalcoholic fatty liver disease (NAFLD), but that “clearly is not the case,” said Dr. Kowdley of the University of Washington, Seattle.

Two recent studies support the beneficial effect of gastroplasty on this spectrum of liver pathology. A 2004 study included 23 patients with nonalcoholic steatohepatitis (NASH) and 12 with simple steatosis. Liver biopsies were obtained from all patients about 2 years after surgery. There were major improvements in lobular steatosis, necroinflammatory changes, and fibrosis; only four patients still fulfilled the criteria for NASH. Improvements were most pronounced in those with metabolic syndrome (Hepatology 2004;39:1647–54).

A 2005 study examined the results of gastric bypass in 16 patients whose mean presurgery weight was 334 pounds. A follow-up liver biopsy was performed about 1 year later. Steatosis had improved in 15 patients, with resolution in 13. Of 15 patients who had inflammation at baseline, 12 showed improvement, and 12 of 14 showed less ballooning. Six of 14 patients with perisinusoidal fibrosis and 6 of 13 with portal fibrosis showed improvement. No patient had worsening of steatosis, inflammation, ballooning, or fibrosis (Obes. Res. 2005;13:1180–6).

NAFLD is part of a histopathologic spectrum of liver injury that ranges from simple steatosis to necroinflammatory changes that may progress to cirrhosis. NASH is associated with increased risk of hepatocellular cancer and liver-related death.

The etiology of these disorders is poorly understood but is thought to be a “two-hit” process beginning with fat accumulation in the liver, most often in the presence of obesity, insulin resistance, or type 2 diabetes. “The 'second hit' is presumed to be any number of processes that contribute to oxidative injury in the liver,” Dr. Kowdley said, and could include oxidative stress that interferes with mitochondrial function.

Most patients with NAFLD are asymptomatic; their disease is discovered when screening tests identify abnormal liver function. Many are obese; studies suggest that about 30% of patients who undergo gastric bypass have the disease. But the pattern of fat deposition is perhaps more important than the patient's weight, Dr. Kowdley said; NAFLD is highly associated with truncal obesity.

On ultrasound, the fatty liver typically appears diffusely hyperechoic in relation to the spleen and kidneys. Computed tomography and magnetic resonance imaging may show focal fat deposits. However, a liver biopsy is the most sensitive and specific means of diagnosis and can differentiate simple steatohepatitis from more advanced stages of the disease in which fibrosis may be present.

There are no approved pharmacologic therapies for NAFLD. Several drugs are under investigation, including metformin and thiazolidinediones.

“Weight loss is one highly recommended method of dealing with NAFLD,” Dr. Kowdley said. “Even a modest amount of weight loss, say 20 pounds, significantly decreases the fasting insulin level and improves liver enzymes, and those improvements are maintained as long as weight loss is maintained. A 40% reduction from initial alanine aminotransferase levels can be achieved.”

All patients with NAFLD should be counseled to lose weight through a combination of diet and exercise. Those with a body mass index (BMI) greater than 30 kg/m

TORONTO — Atomoxetine once a day is as effective as methylphenidate taken twice a day in reducing symptoms of attention-deficit hyperactivity disorder in children, Dr. Yufeng Wang of Beijing Medical University reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

However, the study, funded by Eli Lilly & Co., concluded that treatment-emergent adverse events, including anorexia, nausea, somnolence, dizziness, and vomiting, were significantly more common among those taking atomoxetine.

The study involved a total of 330 children aged 6–16 years from China, Mexico, and Korea who were randomized to either once-daily atomoxetine (0.8–1.8 mg/kg per day) or twice-daily methylphenidate (0.2–0.5 mg/kg per day). Responders were those who experienced at least a 40% reduction from baseline symptom scores as measured by the parents' ADHD Rating Scale. Response rates were 77% for atomoxetine and 81% for methylphenidate—not a statistically significant difference.

The total score changes on the parents' ADHD Rating Scale were similar for atomoxetine and methylphenidate (38 vs. 37, respectively), as were the score changes on the inattention and hyperactivity subscales. Changes on the Connors Parent Rating Scale and the Clinical Global Impressions scale also were similar for both groups.

Side effects were classified as mild to moderate, and tended to occur early and decrease over time. The side effects that were significantly more common in the atomoxetine group than in the methylphenidate group were anorexia (37% vs. 25%), decreased appetite (28% vs. 19%), nausea (20% vs. 10%), somnolence (26% vs. 4%), dizziness (15% vs. 7%), and vomiting (12% vs. 6%).

TORONTO — Atomoxetine once a day is as effective as methylphenidate taken twice a day in reducing symptoms of attention-deficit hyperactivity disorder in children, Dr. Yufeng Wang of Beijing Medical University reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

However, the study, funded by Eli Lilly & Co., concluded that treatment-emergent adverse events, including anorexia, nausea, somnolence, dizziness, and vomiting, were significantly more common among those taking atomoxetine.

The study involved a total of 330 children aged 6–16 years from China, Mexico, and Korea who were randomized to either once-daily atomoxetine (0.8–1.8 mg/kg per day) or twice-daily methylphenidate (0.2–0.5 mg/kg per day). Responders were those who experienced at least a 40% reduction from baseline symptom scores as measured by the parents' ADHD Rating Scale. Response rates were 77% for atomoxetine and 81% for methylphenidate—not a statistically significant difference.

The total score changes on the parents' ADHD Rating Scale were similar for atomoxetine and methylphenidate (38 vs. 37, respectively), as were the score changes on the inattention and hyperactivity subscales. Changes on the Connors Parent Rating Scale and the Clinical Global Impressions scale also were similar for both groups.

Side effects were classified as mild to moderate, and tended to occur early and decrease over time. The side effects that were significantly more common in the atomoxetine group than in the methylphenidate group were anorexia (37% vs. 25%), decreased appetite (28% vs. 19%), nausea (20% vs. 10%), somnolence (26% vs. 4%), dizziness (15% vs. 7%), and vomiting (12% vs. 6%).

TORONTO — Atomoxetine once a day is as effective as methylphenidate taken twice a day in reducing symptoms of attention-deficit hyperactivity disorder in children, Dr. Yufeng Wang of Beijing Medical University reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

However, the study, funded by Eli Lilly & Co., concluded that treatment-emergent adverse events, including anorexia, nausea, somnolence, dizziness, and vomiting, were significantly more common among those taking atomoxetine.

The study involved a total of 330 children aged 6–16 years from China, Mexico, and Korea who were randomized to either once-daily atomoxetine (0.8–1.8 mg/kg per day) or twice-daily methylphenidate (0.2–0.5 mg/kg per day). Responders were those who experienced at least a 40% reduction from baseline symptom scores as measured by the parents' ADHD Rating Scale. Response rates were 77% for atomoxetine and 81% for methylphenidate—not a statistically significant difference.

The total score changes on the parents' ADHD Rating Scale were similar for atomoxetine and methylphenidate (38 vs. 37, respectively), as were the score changes on the inattention and hyperactivity subscales. Changes on the Connors Parent Rating Scale and the Clinical Global Impressions scale also were similar for both groups.

Side effects were classified as mild to moderate, and tended to occur early and decrease over time. The side effects that were significantly more common in the atomoxetine group than in the methylphenidate group were anorexia (37% vs. 25%), decreased appetite (28% vs. 19%), nausea (20% vs. 10%), somnolence (26% vs. 4%), dizziness (15% vs. 7%), and vomiting (12% vs. 6%).

TORONTO — Modafinil is safe and effective in treating pediatric attention-deficit hyperactivity disorder. Symptom scores were twice as high as placebo, according to two posters presented at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

The posters, sponsored by Cephalon Inc., concluded that children tolerated the film-coated tablets well in dosages of up to 425 mg/day. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Those adverse events typically occurred during the first 2 weeks of therapy and decreased thereafter, said Dr. Christopher Kratochvil of the University of Nebraska.

The posters analyzed three multicenter, double-blind studies that included a total of 633 children aged 6–17 years. Two studies were identical 9-week flexible-dosing trials. The third was a 7-week, fixed-dose, placebo-controlled study (340 or 425 mg/day), followed by a 2-week period in which half the modafinil group was switched to placebo without tapering while the other half continued modafinil treatment.

Adverse events were more common in the active group than the placebo group and included insomnia (27% vs. 4%), headache (20% vs. 13%), and decreased appetite (16% vs. 3%).

The adverse events were all classified as mild to moderate. They peaked in the first 2 weeks of treatment and subsequently subsided. No apparent association was found between adverse events and dosage.

There were no significant changes in heart rate or blood pressure between the groups, and the abrupt discontinuation of the drug did not lead to acute withdrawal symptoms or rebound effects.

The drug effectively reduced the symptoms of ADHD, especially hyperactivity and inattention, reported Dr. Joseph Biederman of Massachusetts General Hospital. Effects were consistent whether assessed by physician, parent, or teacher. Physicians assessed almost 50% of the active groups as much improved at the end of treatment, vs. 20% of the placebo group.

TORONTO — Modafinil is safe and effective in treating pediatric attention-deficit hyperactivity disorder. Symptom scores were twice as high as placebo, according to two posters presented at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

The posters, sponsored by Cephalon Inc., concluded that children tolerated the film-coated tablets well in dosages of up to 425 mg/day. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Those adverse events typically occurred during the first 2 weeks of therapy and decreased thereafter, said Dr. Christopher Kratochvil of the University of Nebraska.

The posters analyzed three multicenter, double-blind studies that included a total of 633 children aged 6–17 years. Two studies were identical 9-week flexible-dosing trials. The third was a 7-week, fixed-dose, placebo-controlled study (340 or 425 mg/day), followed by a 2-week period in which half the modafinil group was switched to placebo without tapering while the other half continued modafinil treatment.

Adverse events were more common in the active group than the placebo group and included insomnia (27% vs. 4%), headache (20% vs. 13%), and decreased appetite (16% vs. 3%).

The adverse events were all classified as mild to moderate. They peaked in the first 2 weeks of treatment and subsequently subsided. No apparent association was found between adverse events and dosage.

There were no significant changes in heart rate or blood pressure between the groups, and the abrupt discontinuation of the drug did not lead to acute withdrawal symptoms or rebound effects.

The drug effectively reduced the symptoms of ADHD, especially hyperactivity and inattention, reported Dr. Joseph Biederman of Massachusetts General Hospital. Effects were consistent whether assessed by physician, parent, or teacher. Physicians assessed almost 50% of the active groups as much improved at the end of treatment, vs. 20% of the placebo group.

TORONTO — Modafinil is safe and effective in treating pediatric attention-deficit hyperactivity disorder. Symptom scores were twice as high as placebo, according to two posters presented at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

The posters, sponsored by Cephalon Inc., concluded that children tolerated the film-coated tablets well in dosages of up to 425 mg/day. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Those adverse events typically occurred during the first 2 weeks of therapy and decreased thereafter, said Dr. Christopher Kratochvil of the University of Nebraska.

The posters analyzed three multicenter, double-blind studies that included a total of 633 children aged 6–17 years. Two studies were identical 9-week flexible-dosing trials. The third was a 7-week, fixed-dose, placebo-controlled study (340 or 425 mg/day), followed by a 2-week period in which half the modafinil group was switched to placebo without tapering while the other half continued modafinil treatment.

Adverse events were more common in the active group than the placebo group and included insomnia (27% vs. 4%), headache (20% vs. 13%), and decreased appetite (16% vs. 3%).

The adverse events were all classified as mild to moderate. They peaked in the first 2 weeks of treatment and subsequently subsided. No apparent association was found between adverse events and dosage.

There were no significant changes in heart rate or blood pressure between the groups, and the abrupt discontinuation of the drug did not lead to acute withdrawal symptoms or rebound effects.

The drug effectively reduced the symptoms of ADHD, especially hyperactivity and inattention, reported Dr. Joseph Biederman of Massachusetts General Hospital. Effects were consistent whether assessed by physician, parent, or teacher. Physicians assessed almost 50% of the active groups as much improved at the end of treatment, vs. 20% of the placebo group.

WASHINGTON — Patients with refractory epilepsy may be at increased risk for cardiac arrhythmias and resultant cardiac ischemia during seizures, as well as interictal sinus rhythm pauses, Dr. Maromi Nei reported in a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

In some cases, such arrhythmias may be a contributing factor to sudden unexpected death in epilepsy (SUDEP), said Dr. Nei of the Jefferson Comprehensive Epilepsy Center, Philadelphia, although more study is necessary to confirm this association.

SUDEP accounts for 8%–17% of deaths among people with epilepsy and is most common in those with refractory disease. SUDEP is defined as sudden, unexpected, nontraumatic, nondrowning death in an individual with epilepsy, witnessed or unwitnessed, in which postmortem examination does not reveal an anatomic or toxicologic cause for the death.

Using an implantable cardiac monitoring device, Dr. Nei recorded heart rhythm in 14 patients (mean age 40 years) with refractory epilepsy for a mean of 10 months. Epilepsy was idiopathic generalized in two, symptomatic generalized in three, and partial in nine. They had failed a mean of seven antiepileptic drugs, and eight had failed epilepsy surgery. None of the patients had a history of heart disease.

A subcutaneous cardiac loop recording device was implanted in all patients. The cardiac monitor was programmed to record when the heart rate fell below 30 beats per minute (BPM) or when it exceeded 180 BPM. Patients were asked to activate the device at the time of any seizures, episodic loss of consciousness, presyncope, or palpitations. They also kept diaries documenting these events.

At the conclusion of monitoring, patients had experienced a mean of 37 seizures each (range 2–236). Their mean ictal heart rate was 110 BPM (range 76–198).

Two patients had T wave inversions during their seizures. One patient had ST segment elevation during seizures, and one patient had frequent atrial premature contractions in the postictal period. Sinus arrest of up to 4.8 seconds occurred in one patient during sleep that was not associated with seizure. All other patients had sinus rhythm pauses or sinus tachycardia associated with their seizures. The significance of these rhythm disturbances is unknown, Dr. Nei said in an interview.

The premature atrial contractions are probably not clinically significant, but are consistent with an increase in autonomic stimulation occurring with the seizure, she added.

The case of sinus arrest suggests that there could be an increase in vagal tone that might result in an increased risk for sinus arrest, particularly during sleep. “This is important because SUDEP often occurs during sleep, and this finding suggests that one possible mechanism for SUDEP is sinus arrest,” she said.

WASHINGTON — Patients with refractory epilepsy may be at increased risk for cardiac arrhythmias and resultant cardiac ischemia during seizures, as well as interictal sinus rhythm pauses, Dr. Maromi Nei reported in a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

In some cases, such arrhythmias may be a contributing factor to sudden unexpected death in epilepsy (SUDEP), said Dr. Nei of the Jefferson Comprehensive Epilepsy Center, Philadelphia, although more study is necessary to confirm this association.

SUDEP accounts for 8%–17% of deaths among people with epilepsy and is most common in those with refractory disease. SUDEP is defined as sudden, unexpected, nontraumatic, nondrowning death in an individual with epilepsy, witnessed or unwitnessed, in which postmortem examination does not reveal an anatomic or toxicologic cause for the death.

Using an implantable cardiac monitoring device, Dr. Nei recorded heart rhythm in 14 patients (mean age 40 years) with refractory epilepsy for a mean of 10 months. Epilepsy was idiopathic generalized in two, symptomatic generalized in three, and partial in nine. They had failed a mean of seven antiepileptic drugs, and eight had failed epilepsy surgery. None of the patients had a history of heart disease.

A subcutaneous cardiac loop recording device was implanted in all patients. The cardiac monitor was programmed to record when the heart rate fell below 30 beats per minute (BPM) or when it exceeded 180 BPM. Patients were asked to activate the device at the time of any seizures, episodic loss of consciousness, presyncope, or palpitations. They also kept diaries documenting these events.

At the conclusion of monitoring, patients had experienced a mean of 37 seizures each (range 2–236). Their mean ictal heart rate was 110 BPM (range 76–198).

Two patients had T wave inversions during their seizures. One patient had ST segment elevation during seizures, and one patient had frequent atrial premature contractions in the postictal period. Sinus arrest of up to 4.8 seconds occurred in one patient during sleep that was not associated with seizure. All other patients had sinus rhythm pauses or sinus tachycardia associated with their seizures. The significance of these rhythm disturbances is unknown, Dr. Nei said in an interview.

The premature atrial contractions are probably not clinically significant, but are consistent with an increase in autonomic stimulation occurring with the seizure, she added.

The case of sinus arrest suggests that there could be an increase in vagal tone that might result in an increased risk for sinus arrest, particularly during sleep. “This is important because SUDEP often occurs during sleep, and this finding suggests that one possible mechanism for SUDEP is sinus arrest,” she said.

WASHINGTON — Patients with refractory epilepsy may be at increased risk for cardiac arrhythmias and resultant cardiac ischemia during seizures, as well as interictal sinus rhythm pauses, Dr. Maromi Nei reported in a poster at the joint annual meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

In some cases, such arrhythmias may be a contributing factor to sudden unexpected death in epilepsy (SUDEP), said Dr. Nei of the Jefferson Comprehensive Epilepsy Center, Philadelphia, although more study is necessary to confirm this association.

SUDEP accounts for 8%–17% of deaths among people with epilepsy and is most common in those with refractory disease. SUDEP is defined as sudden, unexpected, nontraumatic, nondrowning death in an individual with epilepsy, witnessed or unwitnessed, in which postmortem examination does not reveal an anatomic or toxicologic cause for the death.

Using an implantable cardiac monitoring device, Dr. Nei recorded heart rhythm in 14 patients (mean age 40 years) with refractory epilepsy for a mean of 10 months. Epilepsy was idiopathic generalized in two, symptomatic generalized in three, and partial in nine. They had failed a mean of seven antiepileptic drugs, and eight had failed epilepsy surgery. None of the patients had a history of heart disease.

A subcutaneous cardiac loop recording device was implanted in all patients. The cardiac monitor was programmed to record when the heart rate fell below 30 beats per minute (BPM) or when it exceeded 180 BPM. Patients were asked to activate the device at the time of any seizures, episodic loss of consciousness, presyncope, or palpitations. They also kept diaries documenting these events.

At the conclusion of monitoring, patients had experienced a mean of 37 seizures each (range 2–236). Their mean ictal heart rate was 110 BPM (range 76–198).

Two patients had T wave inversions during their seizures. One patient had ST segment elevation during seizures, and one patient had frequent atrial premature contractions in the postictal period. Sinus arrest of up to 4.8 seconds occurred in one patient during sleep that was not associated with seizure. All other patients had sinus rhythm pauses or sinus tachycardia associated with their seizures. The significance of these rhythm disturbances is unknown, Dr. Nei said in an interview.

The premature atrial contractions are probably not clinically significant, but are consistent with an increase in autonomic stimulation occurring with the seizure, she added.

The case of sinus arrest suggests that there could be an increase in vagal tone that might result in an increased risk for sinus arrest, particularly during sleep. “This is important because SUDEP often occurs during sleep, and this finding suggests that one possible mechanism for SUDEP is sinus arrest,” she said.

Flu shots are de rigueur for children with neurologic and neuromuscular diseases given their high risk of influenza-related respiratory failure.

“Children with pulmonary disease, cardiac disease, or NNMD [neurologic and neuromuscular disease] had approximately a 10% probability of respiratory failure” during a hospitalization for influenza, Dr. Ron Keren and his colleagues reported. “Having two of the three chronic conditions increased the probability another three- to fourfold” (JAMA 2005;294:2188–94).

Dr. Keren, of the Children's Hospital of Philadelphia, and his associates examined rates of respiratory failure in 745 children and adolescents (aged 21 years and younger) in 2000–2004. Eighty-nine (12%) had an NNMD, most commonly cerebral palsy (40%), seizure disorders (42%), and hydrocephalus/cerebrospinal fluid shunt (30%).

During the study period, 32 children developed respiratory failure; 14 of those had an NNMD, a sixfold increased risk, compared with those with no chronic health problem.

This risk was higher than that associated with pulmonary disease (OR 5.0) or cardiac disease (OR 4.0), both of which are accepted indications for an annual childhood influenza vaccine.

Flu shots are de rigueur for children with neurologic and neuromuscular diseases given their high risk of influenza-related respiratory failure.

“Children with pulmonary disease, cardiac disease, or NNMD [neurologic and neuromuscular disease] had approximately a 10% probability of respiratory failure” during a hospitalization for influenza, Dr. Ron Keren and his colleagues reported. “Having two of the three chronic conditions increased the probability another three- to fourfold” (JAMA 2005;294:2188–94).

Dr. Keren, of the Children's Hospital of Philadelphia, and his associates examined rates of respiratory failure in 745 children and adolescents (aged 21 years and younger) in 2000–2004. Eighty-nine (12%) had an NNMD, most commonly cerebral palsy (40%), seizure disorders (42%), and hydrocephalus/cerebrospinal fluid shunt (30%).

During the study period, 32 children developed respiratory failure; 14 of those had an NNMD, a sixfold increased risk, compared with those with no chronic health problem.

This risk was higher than that associated with pulmonary disease (OR 5.0) or cardiac disease (OR 4.0), both of which are accepted indications for an annual childhood influenza vaccine.

Flu shots are de rigueur for children with neurologic and neuromuscular diseases given their high risk of influenza-related respiratory failure.

“Children with pulmonary disease, cardiac disease, or NNMD [neurologic and neuromuscular disease] had approximately a 10% probability of respiratory failure” during a hospitalization for influenza, Dr. Ron Keren and his colleagues reported. “Having two of the three chronic conditions increased the probability another three- to fourfold” (JAMA 2005;294:2188–94).

Dr. Keren, of the Children's Hospital of Philadelphia, and his associates examined rates of respiratory failure in 745 children and adolescents (aged 21 years and younger) in 2000–2004. Eighty-nine (12%) had an NNMD, most commonly cerebral palsy (40%), seizure disorders (42%), and hydrocephalus/cerebrospinal fluid shunt (30%).

During the study period, 32 children developed respiratory failure; 14 of those had an NNMD, a sixfold increased risk, compared with those with no chronic health problem.

This risk was higher than that associated with pulmonary disease (OR 5.0) or cardiac disease (OR 4.0), both of which are accepted indications for an annual childhood influenza vaccine.

TORONTO — Ziprasidone holds promise as a treatment for childhood bipolar disorder, Dr. Joseph Biederman reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Dr. Biederman of Harvard Medical School, Boston, investigated the drug's effect in an 8-week study of 21 patients aged from 6 to 17 years (mean age 10 years).

All of the children who participated in the study had bipolar disorder. The children were displaying manic, hypomanic, or mixed symptoms, with or without psychoses.

The study participants were not taking any mood stabilizers or any other neuroleptic drugs. At baseline, their mean Young Mania Rating Scale (YMRS) score was 26; their mean IQ was 100.5.

Patients received an initial daily dose of 1 mg/kg ziprasidone, which was titrated upward to 1.5 mg/kg by week 2, and 2 mg/kg by week 3 if tolerated. At the close of the study, the mean daily dose was 56 mg/day.

By the end of week 1, the mean YMRS score had decreased by 8 points. By the end of the study, the mean YMRS score had decreased to 15—a drop of 11 points.

More than half the patients (57%) had a 30% reduction in baseline YMRS scores and were rated as much or very much improved in the Clinical Global Impression scale. One-third of the patients had a YMRS score reduction of 50%.

Comorbid psychiatric symptoms also improved in some patients, Dr. Biederman wrote; 38% had an improvement in depression, 27% improved their attention-deficit hyperactivity disorder symptoms, and 7% of the patients improved their conduct symptoms.

However, he said, only 66% (14) completed the 8-week trial; dropouts were attributable to adverse events (2) and lack of efficacy (5).

The most frequently reported adverse effects experienced by the patients were sedation (46%), headache (38%), and GI problems (34%).

Ziprasidone was not associated with any statistically significant increase in body weight or QTc interval.

The drug has been previously shown safe and effective in adults with bipolar disorder, with limited impact on prolactin levels and weight gain, Dr. Biederman commented.

Dr. Biederman has received grants from Pfizer, which makes the drug. The poster was sponsored by the nonprofit Stanley Medical Research Institute.

TORONTO — Ziprasidone holds promise as a treatment for childhood bipolar disorder, Dr. Joseph Biederman reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Dr. Biederman of Harvard Medical School, Boston, investigated the drug's effect in an 8-week study of 21 patients aged from 6 to 17 years (mean age 10 years).

All of the children who participated in the study had bipolar disorder. The children were displaying manic, hypomanic, or mixed symptoms, with or without psychoses.

The study participants were not taking any mood stabilizers or any other neuroleptic drugs. At baseline, their mean Young Mania Rating Scale (YMRS) score was 26; their mean IQ was 100.5.

Patients received an initial daily dose of 1 mg/kg ziprasidone, which was titrated upward to 1.5 mg/kg by week 2, and 2 mg/kg by week 3 if tolerated. At the close of the study, the mean daily dose was 56 mg/day.

By the end of week 1, the mean YMRS score had decreased by 8 points. By the end of the study, the mean YMRS score had decreased to 15—a drop of 11 points.

More than half the patients (57%) had a 30% reduction in baseline YMRS scores and were rated as much or very much improved in the Clinical Global Impression scale. One-third of the patients had a YMRS score reduction of 50%.

Comorbid psychiatric symptoms also improved in some patients, Dr. Biederman wrote; 38% had an improvement in depression, 27% improved their attention-deficit hyperactivity disorder symptoms, and 7% of the patients improved their conduct symptoms.

However, he said, only 66% (14) completed the 8-week trial; dropouts were attributable to adverse events (2) and lack of efficacy (5).

The most frequently reported adverse effects experienced by the patients were sedation (46%), headache (38%), and GI problems (34%).

Ziprasidone was not associated with any statistically significant increase in body weight or QTc interval.

The drug has been previously shown safe and effective in adults with bipolar disorder, with limited impact on prolactin levels and weight gain, Dr. Biederman commented.

Dr. Biederman has received grants from Pfizer, which makes the drug. The poster was sponsored by the nonprofit Stanley Medical Research Institute.

TORONTO — Ziprasidone holds promise as a treatment for childhood bipolar disorder, Dr. Joseph Biederman reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Dr. Biederman of Harvard Medical School, Boston, investigated the drug's effect in an 8-week study of 21 patients aged from 6 to 17 years (mean age 10 years).

All of the children who participated in the study had bipolar disorder. The children were displaying manic, hypomanic, or mixed symptoms, with or without psychoses.

The study participants were not taking any mood stabilizers or any other neuroleptic drugs. At baseline, their mean Young Mania Rating Scale (YMRS) score was 26; their mean IQ was 100.5.

Patients received an initial daily dose of 1 mg/kg ziprasidone, which was titrated upward to 1.5 mg/kg by week 2, and 2 mg/kg by week 3 if tolerated. At the close of the study, the mean daily dose was 56 mg/day.

By the end of week 1, the mean YMRS score had decreased by 8 points. By the end of the study, the mean YMRS score had decreased to 15—a drop of 11 points.

More than half the patients (57%) had a 30% reduction in baseline YMRS scores and were rated as much or very much improved in the Clinical Global Impression scale. One-third of the patients had a YMRS score reduction of 50%.

Comorbid psychiatric symptoms also improved in some patients, Dr. Biederman wrote; 38% had an improvement in depression, 27% improved their attention-deficit hyperactivity disorder symptoms, and 7% of the patients improved their conduct symptoms.

However, he said, only 66% (14) completed the 8-week trial; dropouts were attributable to adverse events (2) and lack of efficacy (5).

The most frequently reported adverse effects experienced by the patients were sedation (46%), headache (38%), and GI problems (34%).

Ziprasidone was not associated with any statistically significant increase in body weight or QTc interval.

The drug has been previously shown safe and effective in adults with bipolar disorder, with limited impact on prolactin levels and weight gain, Dr. Biederman commented.

Dr. Biederman has received grants from Pfizer, which makes the drug. The poster was sponsored by the nonprofit Stanley Medical Research Institute.

TORONTO — Many children with bipolar disorder experience a lengthy prodromal phase of clinically significant symptoms before their first manic episode; in almost 70% of these children, the prodrome begins with a drop in school functioning, often accompanied by racing thoughts, irritability, and anger, and can last for almost 1 year.

Recognizing such a prodrome could help facilitate early intervention for children at risk of developing bipolar disorder, Dr. Christoph Correll reported at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

“The sufficient duration and severity of this prodrome enables the development of early identification and prevention programs,” wrote Dr. Correll, a psychiatrist at the Zucker Hillside Hospital, Glen Oaks, N.Y. However, “prospective studies are required to validate these findings and to test effective interventions.”

Dr. Correll characterized the onset of bipolar disorder in 51 patients by interviewing the patients and/or their parents with his newly created Bipolar Prodrome Symptoms Scale-Retrospective Version. The questionnaire asks parents and patients to rate 39 putatively prodromal symptoms that can emerge before a syndromal manic or hypomanic episode.

The scale—an in-person structured interview with patient or parent alone—takes between 1 and 1.5 hours to complete. It was developed based on DSM-IV criteria for major depressive disorder and bipolar disorder, a review of the literature, input from experts in the areas of schizophrenia prodrome and bipolar disorder, and open questioning of young patients and their caregivers.

Dr. Correll also drew the symptoms that the scale assesses from several retrospective studies that have identified some possibly prodromal traits, including depressed mood or hopelessness, hyperactivity, mood swings, increased or decreased energy, irritability or anger dyscontrol, argumentativeness, decreased sleep, crying spells, inappropriate behaviors, and overtalkativeness.

The patients' mean age was 16 years; the mean age at first manic episode was 13 years. The patients experienced a mean of 13 of the prodromal symptoms, which preceded the first full manic episode by nearly 1 year.

In more than half of the patients, the most commonly reported symptoms that were at least moderately severe were a drop in school functioning, irritability or anger, racing thoughts, mood swings, inattention, depressed mood, and anger outbursts or tantrums. At least moderately severe symptoms of increased energy, psychomotor agitation, overtalkativeness, and social isolation occurred in more than 40% of patients.

The most common presenting symptoms were a drop in school functioning, mood swings, depressed mood, irritability or anger, social isolation, and racing thoughts. About one in five patients reported presenting symptoms of oppositionality, anhedonia, being overly cheerful, psychomotor agitation, or inattention.

The lag between first manic episode and bipolar disorder diagnosis was about 20 months, but the lag between the onset of prodromal symptoms and diagnosis was about twice that long—a mean of 41 months. In most patients (59%), the prodromal onset was slow and marked by gradual deterioration; 29% of patients experienced a slow onset with quick deterioration, while only 12% had a rapid onset of illness.

The newly developed scale will be useful not only in assessing a possible prodrome, but in research as well, Dr. Correll said in an interview. “It can be used in future studies to determine different patterns of symptom onset and contributing factors to symptom onset, as well as to identify characteristics that may define a person who may be at ultrahigh risk for the development of bipolar disorder.”

He is also working on a prospective version of the scale, which he hopes will be a valuable tool for predicting conversion to bipolar disorder in patients considered to be at risk for the disorder.

In most patients (59%), the prodromal onset was slow and marked by gradual deterioration. DR. CORRELL

TORONTO — Many children with bipolar disorder experience a lengthy prodromal phase of clinically significant symptoms before their first manic episode; in almost 70% of these children, the prodrome begins with a drop in school functioning, often accompanied by racing thoughts, irritability, and anger, and can last for almost 1 year.

Recognizing such a prodrome could help facilitate early intervention for children at risk of developing bipolar disorder, Dr. Christoph Correll reported at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

“The sufficient duration and severity of this prodrome enables the development of early identification and prevention programs,” wrote Dr. Correll, a psychiatrist at the Zucker Hillside Hospital, Glen Oaks, N.Y. However, “prospective studies are required to validate these findings and to test effective interventions.”

Dr. Correll characterized the onset of bipolar disorder in 51 patients by interviewing the patients and/or their parents with his newly created Bipolar Prodrome Symptoms Scale-Retrospective Version. The questionnaire asks parents and patients to rate 39 putatively prodromal symptoms that can emerge before a syndromal manic or hypomanic episode.

The scale—an in-person structured interview with patient or parent alone—takes between 1 and 1.5 hours to complete. It was developed based on DSM-IV criteria for major depressive disorder and bipolar disorder, a review of the literature, input from experts in the areas of schizophrenia prodrome and bipolar disorder, and open questioning of young patients and their caregivers.

Dr. Correll also drew the symptoms that the scale assesses from several retrospective studies that have identified some possibly prodromal traits, including depressed mood or hopelessness, hyperactivity, mood swings, increased or decreased energy, irritability or anger dyscontrol, argumentativeness, decreased sleep, crying spells, inappropriate behaviors, and overtalkativeness.

The patients' mean age was 16 years; the mean age at first manic episode was 13 years. The patients experienced a mean of 13 of the prodromal symptoms, which preceded the first full manic episode by nearly 1 year.

In more than half of the patients, the most commonly reported symptoms that were at least moderately severe were a drop in school functioning, irritability or anger, racing thoughts, mood swings, inattention, depressed mood, and anger outbursts or tantrums. At least moderately severe symptoms of increased energy, psychomotor agitation, overtalkativeness, and social isolation occurred in more than 40% of patients.

The most common presenting symptoms were a drop in school functioning, mood swings, depressed mood, irritability or anger, social isolation, and racing thoughts. About one in five patients reported presenting symptoms of oppositionality, anhedonia, being overly cheerful, psychomotor agitation, or inattention.

The lag between first manic episode and bipolar disorder diagnosis was about 20 months, but the lag between the onset of prodromal symptoms and diagnosis was about twice that long—a mean of 41 months. In most patients (59%), the prodromal onset was slow and marked by gradual deterioration; 29% of patients experienced a slow onset with quick deterioration, while only 12% had a rapid onset of illness.

The newly developed scale will be useful not only in assessing a possible prodrome, but in research as well, Dr. Correll said in an interview. “It can be used in future studies to determine different patterns of symptom onset and contributing factors to symptom onset, as well as to identify characteristics that may define a person who may be at ultrahigh risk for the development of bipolar disorder.”

He is also working on a prospective version of the scale, which he hopes will be a valuable tool for predicting conversion to bipolar disorder in patients considered to be at risk for the disorder.

In most patients (59%), the prodromal onset was slow and marked by gradual deterioration. DR. CORRELL

TORONTO — Many children with bipolar disorder experience a lengthy prodromal phase of clinically significant symptoms before their first manic episode; in almost 70% of these children, the prodrome begins with a drop in school functioning, often accompanied by racing thoughts, irritability, and anger, and can last for almost 1 year.

Recognizing such a prodrome could help facilitate early intervention for children at risk of developing bipolar disorder, Dr. Christoph Correll reported at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

“The sufficient duration and severity of this prodrome enables the development of early identification and prevention programs,” wrote Dr. Correll, a psychiatrist at the Zucker Hillside Hospital, Glen Oaks, N.Y. However, “prospective studies are required to validate these findings and to test effective interventions.”

Dr. Correll characterized the onset of bipolar disorder in 51 patients by interviewing the patients and/or their parents with his newly created Bipolar Prodrome Symptoms Scale-Retrospective Version. The questionnaire asks parents and patients to rate 39 putatively prodromal symptoms that can emerge before a syndromal manic or hypomanic episode.

The scale—an in-person structured interview with patient or parent alone—takes between 1 and 1.5 hours to complete. It was developed based on DSM-IV criteria for major depressive disorder and bipolar disorder, a review of the literature, input from experts in the areas of schizophrenia prodrome and bipolar disorder, and open questioning of young patients and their caregivers.

Dr. Correll also drew the symptoms that the scale assesses from several retrospective studies that have identified some possibly prodromal traits, including depressed mood or hopelessness, hyperactivity, mood swings, increased or decreased energy, irritability or anger dyscontrol, argumentativeness, decreased sleep, crying spells, inappropriate behaviors, and overtalkativeness.

The patients' mean age was 16 years; the mean age at first manic episode was 13 years. The patients experienced a mean of 13 of the prodromal symptoms, which preceded the first full manic episode by nearly 1 year.

In more than half of the patients, the most commonly reported symptoms that were at least moderately severe were a drop in school functioning, irritability or anger, racing thoughts, mood swings, inattention, depressed mood, and anger outbursts or tantrums. At least moderately severe symptoms of increased energy, psychomotor agitation, overtalkativeness, and social isolation occurred in more than 40% of patients.

The most common presenting symptoms were a drop in school functioning, mood swings, depressed mood, irritability or anger, social isolation, and racing thoughts. About one in five patients reported presenting symptoms of oppositionality, anhedonia, being overly cheerful, psychomotor agitation, or inattention.

The lag between first manic episode and bipolar disorder diagnosis was about 20 months, but the lag between the onset of prodromal symptoms and diagnosis was about twice that long—a mean of 41 months. In most patients (59%), the prodromal onset was slow and marked by gradual deterioration; 29% of patients experienced a slow onset with quick deterioration, while only 12% had a rapid onset of illness.

The newly developed scale will be useful not only in assessing a possible prodrome, but in research as well, Dr. Correll said in an interview. “It can be used in future studies to determine different patterns of symptom onset and contributing factors to symptom onset, as well as to identify characteristics that may define a person who may be at ultrahigh risk for the development of bipolar disorder.”

He is also working on a prospective version of the scale, which he hopes will be a valuable tool for predicting conversion to bipolar disorder in patients considered to be at risk for the disorder.

In most patients (59%), the prodromal onset was slow and marked by gradual deterioration. DR. CORRELL

The longer a woman breast-feeds her offspring, the less likely she is to develop type 2 diabetes, Dr. Alison M. Stuebe, and her colleagues have reported.

Their analysis of more than 157,000 women concluded that every year of lactation results in a decreased risk of up to 15% for developing the disease. However, the association wasn't significant for women whose last child was born more than 15 years ago, said Dr. Stuebe of Brigham and Women's Hospital, Boston (JAMA 2005;294:2601-10)

The researchers examined lactation and disease occurrence in women enrolled in the two national Nurses' Health Studies. The studies provided more than 2 million person-years of follow-up from 1986 to 2002.

The Nurses' Health Study (NHS I) included 83,585 women; there were 5,145 incident cases of type 2 diabetes. The NHS II included 73,418 women; there were 1,132 incident cases of type 2 diabetes. In both studies, there was a slight, but significant, inverse association between length of lactation and disease risk.

However, when the researchers analyzed the groups by length of time since giving birth, the impact of breast-feeding became more apparent. Among 857 women who had given birth within the last 15 years, the risk reduction for each year of lactation was 15% in the NHS I and 14% in the NHS II. This association was stronger when women breast-fed for a total of at least 6 months. In the NHS I, the risk reduction was 26% for a cumulative lactation of up to 6 months, 36% for cumulative lactation of up to 1 year, and 53% for cumulative lactation of 23 months or more. The numbers were similar for women in the NHS II.

However, among women who reported their last birth more than 15 years ago, there was no association between the duration of lactation and diabetes. Likewise, there was no association between lactation and disease risk in women with gestational diabetes.

The researchers also found that pharmacological suppression of lactation was associated with an increased risk of developing type 2 diabetes. There was a 46% increased risk of disease in women who used medication to suppress lactation, compared with women who never breast-fed and did not use this type of medication.

The cause of this association is unknown. The investigators suggested that bromocriptine may disrupt mechanisms of appetite regulation or that a choice to suppress lactation may be associated with other behaviors that increase the risk of diabetes.

The decrease in development of diabetes among women who have breast-fed appears linked to lactation's effect on insulin resistance, the researchers said. Studies have shown that lactation is associated with improved glucose tolerance and fasting glucose levels.

The longer a woman breast-feeds her offspring, the less likely she is to develop type 2 diabetes, Dr. Alison M. Stuebe, and her colleagues have reported.

Their analysis of more than 157,000 women concluded that every year of lactation results in a decreased risk of up to 15% for developing the disease. However, the association wasn't significant for women whose last child was born more than 15 years ago, said Dr. Stuebe of Brigham and Women's Hospital, Boston (JAMA 2005;294:2601-10)

The researchers examined lactation and disease occurrence in women enrolled in the two national Nurses' Health Studies. The studies provided more than 2 million person-years of follow-up from 1986 to 2002.

The Nurses' Health Study (NHS I) included 83,585 women; there were 5,145 incident cases of type 2 diabetes. The NHS II included 73,418 women; there were 1,132 incident cases of type 2 diabetes. In both studies, there was a slight, but significant, inverse association between length of lactation and disease risk.

However, when the researchers analyzed the groups by length of time since giving birth, the impact of breast-feeding became more apparent. Among 857 women who had given birth within the last 15 years, the risk reduction for each year of lactation was 15% in the NHS I and 14% in the NHS II. This association was stronger when women breast-fed for a total of at least 6 months. In the NHS I, the risk reduction was 26% for a cumulative lactation of up to 6 months, 36% for cumulative lactation of up to 1 year, and 53% for cumulative lactation of 23 months or more. The numbers were similar for women in the NHS II.

However, among women who reported their last birth more than 15 years ago, there was no association between the duration of lactation and diabetes. Likewise, there was no association between lactation and disease risk in women with gestational diabetes.

The researchers also found that pharmacological suppression of lactation was associated with an increased risk of developing type 2 diabetes. There was a 46% increased risk of disease in women who used medication to suppress lactation, compared with women who never breast-fed and did not use this type of medication.

The cause of this association is unknown. The investigators suggested that bromocriptine may disrupt mechanisms of appetite regulation or that a choice to suppress lactation may be associated with other behaviors that increase the risk of diabetes.

The decrease in development of diabetes among women who have breast-fed appears linked to lactation's effect on insulin resistance, the researchers said. Studies have shown that lactation is associated with improved glucose tolerance and fasting glucose levels.

The longer a woman breast-feeds her offspring, the less likely she is to develop type 2 diabetes, Dr. Alison M. Stuebe, and her colleagues have reported.

Their analysis of more than 157,000 women concluded that every year of lactation results in a decreased risk of up to 15% for developing the disease. However, the association wasn't significant for women whose last child was born more than 15 years ago, said Dr. Stuebe of Brigham and Women's Hospital, Boston (JAMA 2005;294:2601-10)

The researchers examined lactation and disease occurrence in women enrolled in the two national Nurses' Health Studies. The studies provided more than 2 million person-years of follow-up from 1986 to 2002.

The Nurses' Health Study (NHS I) included 83,585 women; there were 5,145 incident cases of type 2 diabetes. The NHS II included 73,418 women; there were 1,132 incident cases of type 2 diabetes. In both studies, there was a slight, but significant, inverse association between length of lactation and disease risk.

However, when the researchers analyzed the groups by length of time since giving birth, the impact of breast-feeding became more apparent. Among 857 women who had given birth within the last 15 years, the risk reduction for each year of lactation was 15% in the NHS I and 14% in the NHS II. This association was stronger when women breast-fed for a total of at least 6 months. In the NHS I, the risk reduction was 26% for a cumulative lactation of up to 6 months, 36% for cumulative lactation of up to 1 year, and 53% for cumulative lactation of 23 months or more. The numbers were similar for women in the NHS II.

However, among women who reported their last birth more than 15 years ago, there was no association between the duration of lactation and diabetes. Likewise, there was no association between lactation and disease risk in women with gestational diabetes.

The researchers also found that pharmacological suppression of lactation was associated with an increased risk of developing type 2 diabetes. There was a 46% increased risk of disease in women who used medication to suppress lactation, compared with women who never breast-fed and did not use this type of medication.

The cause of this association is unknown. The investigators suggested that bromocriptine may disrupt mechanisms of appetite regulation or that a choice to suppress lactation may be associated with other behaviors that increase the risk of diabetes.

The decrease in development of diabetes among women who have breast-fed appears linked to lactation's effect on insulin resistance, the researchers said. Studies have shown that lactation is associated with improved glucose tolerance and fasting glucose levels.

TORONTO – Impulsive-affective conduct disorder responds better to medication than does predatory conduct disorder, Dr. Robert Findling said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

“We need to do better by these children,” said Dr. Findling of Case Western Reserve University, Cleveland. “If you catch them early, before they are hardened by their behavior, you can help them. Young children with conduct disorder [CD] often say they know teachers and other kids think they are bad, and they don't want to be bad. No child deserves to live like that.”

Before deciding on a trial of medication, it's important to characterize the type of conduct disorder a patient presents. Both types are more prevalent in males and often comorbid with depression, anxiety, learning disabilities, or attention-deficit hyperactivity disorder (ADHD). Both types are associated with poor long-term outcomes. “This is a malignant condition. It's pervasive, pernicious, and associated with violence and high rates of antisocial behavior, incarceration, and substance abuse. This is not just a kid being dysfunctional,” he said.

Impulsive-affective CD involves reactive, unplanned, uncontrolled acts of aggression. The child may damage his own property or expose himself to physical harm. He loses control in front of other people and fights without purpose, often against someone stronger. He might express remorse after an explosion.

Predatory CD is a different matter, Dr. Findling said. “This is the kid who will beat somebody up for milk money. This person is quite different from the kid who explodes over a minor provocation.”

The aggressive acts are planned, controlled, and often concealed. The child is very careful to protect himself from harm in the incident and tries to plan it so that he profits in some way. Theft is often a motive. The child may say he is proud of his behavior.

Methylphenidate has been shown effective in CD, decreasing aggression scores significantly, compared with placebo (Arch. Gen. Psychiatry 1997;54:1073–80). Lithium has also been shown effective, “although it has never been embraced as a treatment due to the adverse events in this group,” Dr. Findling said. Those include nausea, vomiting, and urinary frequency.

In 2003, researchers concluded that divalproex was also effective. A 7-week study randomized children with CD to either low or high doses of the drug. The high dose (1,000 mg/day) was more effective in improving self-reported impulse control and self-restraint; almost 60% of those in the high-dose group were much or very much improved, compared with fewer than 10% of those in the low-dose group. Side effects were mild and transient (J. Clin. Psychiatry 2003;64:1183–91).

Many studies detail the benefits of risperidone (Risperdal), Dr. Findling said. A 2002 placebo-controlled trial concluded that a low dose of risperidone (1.16 mg/day) was significantly better than placebo in improving symptoms of CD in children with subaverage IQ and disruptive behavior disorder. Almost 80% of the active group was improved at the end of the trial.

“The magnitude of the dose is important here. This is lower than the dose prescribed by many U.S. providers,” he said. The most common side effects were mild, transient sedation and headache.

Two recent long-term trials of risperidone suggest that the benefit is durable, he said. An open-label trial of 107 children with CD concluded that the improvement was maintained on the same dose over 48 weeks (Am. J. Psychiatry 2004;161:677–84). A larger study, which looked at the effect in 504 children over 1 year, reached the same conclusion (J. Am. Acad. Child. Adolesc. Psychiatry 2005;44:64–72).

Risperidone is also effective in children who start on a psychostimulant but retain problematic aggression; it can be used effectively in children on a stimulant for ADHD. “The stimulant doesn't decrease the effectiveness of risperidone,” he said.

Some pilot studies suggest olanzapine (Zyprexa) and aripiprazole (Abilify) may have beneficial effects on aggression as well. A 2004 study examined olanzapine for aggression and tics in 10 children with Tourette's syndrome. The drug effectively reduced aggression and tic severity, and was well tolerated (J. Child. Adolesc. Psychopharmacol. 2004:14:255–66).

Dr. Findling studied aripiprazole specifically for its effectiveness in CD. “Over a very short time in a very aggressive group of people, we saw a very substantial response,” he said (Int. J. Neuropsychopharmacol. 2004;7:[suppl. 1]:S440).

Adverse events included dyspepsia and persistent emesis, which decreased when the dosing was adjusted. “We started out basing the dosage on weight-adjusted adult data and learned that this was not very well tolerated,” Dr. Findling said. “So we used a lower dose and got a better side effect profile.”

TORONTO – Impulsive-affective conduct disorder responds better to medication than does predatory conduct disorder, Dr. Robert Findling said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

“We need to do better by these children,” said Dr. Findling of Case Western Reserve University, Cleveland. “If you catch them early, before they are hardened by their behavior, you can help them. Young children with conduct disorder [CD] often say they know teachers and other kids think they are bad, and they don't want to be bad. No child deserves to live like that.”

Before deciding on a trial of medication, it's important to characterize the type of conduct disorder a patient presents. Both types are more prevalent in males and often comorbid with depression, anxiety, learning disabilities, or attention-deficit hyperactivity disorder (ADHD). Both types are associated with poor long-term outcomes. “This is a malignant condition. It's pervasive, pernicious, and associated with violence and high rates of antisocial behavior, incarceration, and substance abuse. This is not just a kid being dysfunctional,” he said.

Impulsive-affective CD involves reactive, unplanned, uncontrolled acts of aggression. The child may damage his own property or expose himself to physical harm. He loses control in front of other people and fights without purpose, often against someone stronger. He might express remorse after an explosion.

Predatory CD is a different matter, Dr. Findling said. “This is the kid who will beat somebody up for milk money. This person is quite different from the kid who explodes over a minor provocation.”

The aggressive acts are planned, controlled, and often concealed. The child is very careful to protect himself from harm in the incident and tries to plan it so that he profits in some way. Theft is often a motive. The child may say he is proud of his behavior.

Methylphenidate has been shown effective in CD, decreasing aggression scores significantly, compared with placebo (Arch. Gen. Psychiatry 1997;54:1073–80). Lithium has also been shown effective, “although it has never been embraced as a treatment due to the adverse events in this group,” Dr. Findling said. Those include nausea, vomiting, and urinary frequency.

In 2003, researchers concluded that divalproex was also effective. A 7-week study randomized children with CD to either low or high doses of the drug. The high dose (1,000 mg/day) was more effective in improving self-reported impulse control and self-restraint; almost 60% of those in the high-dose group were much or very much improved, compared with fewer than 10% of those in the low-dose group. Side effects were mild and transient (J. Clin. Psychiatry 2003;64:1183–91).

Many studies detail the benefits of risperidone (Risperdal), Dr. Findling said. A 2002 placebo-controlled trial concluded that a low dose of risperidone (1.16 mg/day) was significantly better than placebo in improving symptoms of CD in children with subaverage IQ and disruptive behavior disorder. Almost 80% of the active group was improved at the end of the trial.

“The magnitude of the dose is important here. This is lower than the dose prescribed by many U.S. providers,” he said. The most common side effects were mild, transient sedation and headache.

Two recent long-term trials of risperidone suggest that the benefit is durable, he said. An open-label trial of 107 children with CD concluded that the improvement was maintained on the same dose over 48 weeks (Am. J. Psychiatry 2004;161:677–84). A larger study, which looked at the effect in 504 children over 1 year, reached the same conclusion (J. Am. Acad. Child. Adolesc. Psychiatry 2005;44:64–72).

Risperidone is also effective in children who start on a psychostimulant but retain problematic aggression; it can be used effectively in children on a stimulant for ADHD. “The stimulant doesn't decrease the effectiveness of risperidone,” he said.

Some pilot studies suggest olanzapine (Zyprexa) and aripiprazole (Abilify) may have beneficial effects on aggression as well. A 2004 study examined olanzapine for aggression and tics in 10 children with Tourette's syndrome. The drug effectively reduced aggression and tic severity, and was well tolerated (J. Child. Adolesc. Psychopharmacol. 2004:14:255–66).

Dr. Findling studied aripiprazole specifically for its effectiveness in CD. “Over a very short time in a very aggressive group of people, we saw a very substantial response,” he said (Int. J. Neuropsychopharmacol. 2004;7:[suppl. 1]:S440).

Adverse events included dyspepsia and persistent emesis, which decreased when the dosing was adjusted. “We started out basing the dosage on weight-adjusted adult data and learned that this was not very well tolerated,” Dr. Findling said. “So we used a lower dose and got a better side effect profile.”

TORONTO – Impulsive-affective conduct disorder responds better to medication than does predatory conduct disorder, Dr. Robert Findling said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

“We need to do better by these children,” said Dr. Findling of Case Western Reserve University, Cleveland. “If you catch them early, before they are hardened by their behavior, you can help them. Young children with conduct disorder [CD] often say they know teachers and other kids think they are bad, and they don't want to be bad. No child deserves to live like that.”

Before deciding on a trial of medication, it's important to characterize the type of conduct disorder a patient presents. Both types are more prevalent in males and often comorbid with depression, anxiety, learning disabilities, or attention-deficit hyperactivity disorder (ADHD). Both types are associated with poor long-term outcomes. “This is a malignant condition. It's pervasive, pernicious, and associated with violence and high rates of antisocial behavior, incarceration, and substance abuse. This is not just a kid being dysfunctional,” he said.

Impulsive-affective CD involves reactive, unplanned, uncontrolled acts of aggression. The child may damage his own property or expose himself to physical harm. He loses control in front of other people and fights without purpose, often against someone stronger. He might express remorse after an explosion.

Predatory CD is a different matter, Dr. Findling said. “This is the kid who will beat somebody up for milk money. This person is quite different from the kid who explodes over a minor provocation.”

The aggressive acts are planned, controlled, and often concealed. The child is very careful to protect himself from harm in the incident and tries to plan it so that he profits in some way. Theft is often a motive. The child may say he is proud of his behavior.

Methylphenidate has been shown effective in CD, decreasing aggression scores significantly, compared with placebo (Arch. Gen. Psychiatry 1997;54:1073–80). Lithium has also been shown effective, “although it has never been embraced as a treatment due to the adverse events in this group,” Dr. Findling said. Those include nausea, vomiting, and urinary frequency.

In 2003, researchers concluded that divalproex was also effective. A 7-week study randomized children with CD to either low or high doses of the drug. The high dose (1,000 mg/day) was more effective in improving self-reported impulse control and self-restraint; almost 60% of those in the high-dose group were much or very much improved, compared with fewer than 10% of those in the low-dose group. Side effects were mild and transient (J. Clin. Psychiatry 2003;64:1183–91).

Many studies detail the benefits of risperidone (Risperdal), Dr. Findling said. A 2002 placebo-controlled trial concluded that a low dose of risperidone (1.16 mg/day) was significantly better than placebo in improving symptoms of CD in children with subaverage IQ and disruptive behavior disorder. Almost 80% of the active group was improved at the end of the trial.

“The magnitude of the dose is important here. This is lower than the dose prescribed by many U.S. providers,” he said. The most common side effects were mild, transient sedation and headache.

Two recent long-term trials of risperidone suggest that the benefit is durable, he said. An open-label trial of 107 children with CD concluded that the improvement was maintained on the same dose over 48 weeks (Am. J. Psychiatry 2004;161:677–84). A larger study, which looked at the effect in 504 children over 1 year, reached the same conclusion (J. Am. Acad. Child. Adolesc. Psychiatry 2005;44:64–72).

Risperidone is also effective in children who start on a psychostimulant but retain problematic aggression; it can be used effectively in children on a stimulant for ADHD. “The stimulant doesn't decrease the effectiveness of risperidone,” he said.

Some pilot studies suggest olanzapine (Zyprexa) and aripiprazole (Abilify) may have beneficial effects on aggression as well. A 2004 study examined olanzapine for aggression and tics in 10 children with Tourette's syndrome. The drug effectively reduced aggression and tic severity, and was well tolerated (J. Child. Adolesc. Psychopharmacol. 2004:14:255–66).

Dr. Findling studied aripiprazole specifically for its effectiveness in CD. “Over a very short time in a very aggressive group of people, we saw a very substantial response,” he said (Int. J. Neuropsychopharmacol. 2004;7:[suppl. 1]:S440).

Adverse events included dyspepsia and persistent emesis, which decreased when the dosing was adjusted. “We started out basing the dosage on weight-adjusted adult data and learned that this was not very well tolerated,” Dr. Findling said. “So we used a lower dose and got a better side effect profile.”

TORONTO – A sudden, severe onset of childhood obsessive-compulsive disorder with tics should prompt a throat culture for group A streptococcus, Dr. Tanya Murphy said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Considerable controversy surrounding the issue persists. But enough evidence exists to suggest a link between acute strep infections and the onset of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), said Dr. Murphy, director of the Child Tic and Anxiety Disorder Clinic, University of Florida, Gainesville.

“There are different opinions on what to do and what to believe,” she said. But a throat culture is an easy, noninvasive method of exploring the possibility of an infectious link.

The OCD that children develop with a strep infection looks quite different from the chronic course usually observed. “The onset is sudden and dramatic,” she said. “The illness follows an episodic or sawtooth course that's marked by changes in strep titers. During exacerbations, you will see a positive culture or rising titers, and during prolonged remission, the titers will fall.”

The OCD is often accompanied by choreiform movements, tics, and comorbid symptoms, including emotional lability, separation anxiety, nocturnal enuresis, and change in school performance. Some children with PANDAS may not have a positive strep throat culture, however. In these cases, serial strep titers may give evidence of a subclinical infection. If strep is present, children should take a full course of antibiotics and return for a repeat culture shortly after the antibiotic is completed.

PANDAS appears to be at the center of a convergence of three factors, Dr. Murphy said: a group A strep infection, genetic predisposition (familial OCD, Tourette's syndrome, or rheumatoid fever, including Sydenham's chorea), and an environmental stress factor such as a central nervous system injury or coinfection. The incidence peaks at ages 5–12 years–the same ages in which strep infections peak.

Dr. Murphy presented the results of a prospective study of 25 children, aged 7–17 years, with typical OCD and tics. The children were assessed every 6 weeks and had at least 6 consecutive assessments; strep titers were taken at each visit. Fifteen children exhibited an episodic or sawtooth disease course. Almost 60% of the episodic group had elevated group A strep titers on all of their visits, while 60% of the steady disease course group had no elevated titers at any time, suggesting that those with a PANDAS-like course have had more frequent undetected strep infections or prolonged immune reaction to past strep infections.

Those with episodic disease were also more likely to have exacerbations in the fall and winter, concurrent with the seasonal rise in strep infections. The children in the episodic group were more likely to be male (67% vs. 30%) and have attention-deficit hyperactivity disorder (73% vs. 40%), compared with those in the steady course group.

“Unlike its namesake, however, PANDAS isn't all black and white,” Dr. Murphy said. There have been few reports that antibiotics for children suspected of having the disorder improved their OCD or tic symptoms. Definitive studies still need to be conducted to clarify the impact of antibiotic treatment on symptoms.

In a 2005 study, 23 children with PANDAS received either azithromycin or penicillin prophylaxis. The drugs decreased additional strep infections and neuropsychiatric symptom exacerbations (Biol. Psychiatry 2005;57:788–92).

In 2002, a prospective study found that children with PANDAS experienced OCD symptom resolution after receiving antibiotics at the sentinel OCD episode (Arch. Pediatr. Adolesc. Med. 2002;156:356–61).

An early clinical trial involving the use of prophylactic penicillin for PANDAS revealed no conclusive evidence that the antibiotic reduced clinical exacerbation. However, the sample size was small (37 subjects), the treatment arm was brief, and the lack of efficacy may have been attributable to the failure of antibiotic therapy to eliminate streptococcal colonization in the patients enrolled in the study, Dr. Murphy said. Since then, investigators have reported improvement in neuropsychiatric symptoms with antibiotic treatment in patients presenting with PANDAS. Difficulties with study design and the small sample size of these early antibiotic trials limit the clinical influence of their findings.

TORONTO – A sudden, severe onset of childhood obsessive-compulsive disorder with tics should prompt a throat culture for group A streptococcus, Dr. Tanya Murphy said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Considerable controversy surrounding the issue persists. But enough evidence exists to suggest a link between acute strep infections and the onset of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), said Dr. Murphy, director of the Child Tic and Anxiety Disorder Clinic, University of Florida, Gainesville.

“There are different opinions on what to do and what to believe,” she said. But a throat culture is an easy, noninvasive method of exploring the possibility of an infectious link.

The OCD that children develop with a strep infection looks quite different from the chronic course usually observed. “The onset is sudden and dramatic,” she said. “The illness follows an episodic or sawtooth course that's marked by changes in strep titers. During exacerbations, you will see a positive culture or rising titers, and during prolonged remission, the titers will fall.”

The OCD is often accompanied by choreiform movements, tics, and comorbid symptoms, including emotional lability, separation anxiety, nocturnal enuresis, and change in school performance. Some children with PANDAS may not have a positive strep throat culture, however. In these cases, serial strep titers may give evidence of a subclinical infection. If strep is present, children should take a full course of antibiotics and return for a repeat culture shortly after the antibiotic is completed.

PANDAS appears to be at the center of a convergence of three factors, Dr. Murphy said: a group A strep infection, genetic predisposition (familial OCD, Tourette's syndrome, or rheumatoid fever, including Sydenham's chorea), and an environmental stress factor such as a central nervous system injury or coinfection. The incidence peaks at ages 5–12 years–the same ages in which strep infections peak.

Dr. Murphy presented the results of a prospective study of 25 children, aged 7–17 years, with typical OCD and tics. The children were assessed every 6 weeks and had at least 6 consecutive assessments; strep titers were taken at each visit. Fifteen children exhibited an episodic or sawtooth disease course. Almost 60% of the episodic group had elevated group A strep titers on all of their visits, while 60% of the steady disease course group had no elevated titers at any time, suggesting that those with a PANDAS-like course have had more frequent undetected strep infections or prolonged immune reaction to past strep infections.

Those with episodic disease were also more likely to have exacerbations in the fall and winter, concurrent with the seasonal rise in strep infections. The children in the episodic group were more likely to be male (67% vs. 30%) and have attention-deficit hyperactivity disorder (73% vs. 40%), compared with those in the steady course group.

“Unlike its namesake, however, PANDAS isn't all black and white,” Dr. Murphy said. There have been few reports that antibiotics for children suspected of having the disorder improved their OCD or tic symptoms. Definitive studies still need to be conducted to clarify the impact of antibiotic treatment on symptoms.

In a 2005 study, 23 children with PANDAS received either azithromycin or penicillin prophylaxis. The drugs decreased additional strep infections and neuropsychiatric symptom exacerbations (Biol. Psychiatry 2005;57:788–92).

In 2002, a prospective study found that children with PANDAS experienced OCD symptom resolution after receiving antibiotics at the sentinel OCD episode (Arch. Pediatr. Adolesc. Med. 2002;156:356–61).

An early clinical trial involving the use of prophylactic penicillin for PANDAS revealed no conclusive evidence that the antibiotic reduced clinical exacerbation. However, the sample size was small (37 subjects), the treatment arm was brief, and the lack of efficacy may have been attributable to the failure of antibiotic therapy to eliminate streptococcal colonization in the patients enrolled in the study, Dr. Murphy said. Since then, investigators have reported improvement in neuropsychiatric symptoms with antibiotic treatment in patients presenting with PANDAS. Difficulties with study design and the small sample size of these early antibiotic trials limit the clinical influence of their findings.

TORONTO – A sudden, severe onset of childhood obsessive-compulsive disorder with tics should prompt a throat culture for group A streptococcus, Dr. Tanya Murphy said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Considerable controversy surrounding the issue persists. But enough evidence exists to suggest a link between acute strep infections and the onset of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), said Dr. Murphy, director of the Child Tic and Anxiety Disorder Clinic, University of Florida, Gainesville.

“There are different opinions on what to do and what to believe,” she said. But a throat culture is an easy, noninvasive method of exploring the possibility of an infectious link.

The OCD that children develop with a strep infection looks quite different from the chronic course usually observed. “The onset is sudden and dramatic,” she said. “The illness follows an episodic or sawtooth course that's marked by changes in strep titers. During exacerbations, you will see a positive culture or rising titers, and during prolonged remission, the titers will fall.”

The OCD is often accompanied by choreiform movements, tics, and comorbid symptoms, including emotional lability, separation anxiety, nocturnal enuresis, and change in school performance. Some children with PANDAS may not have a positive strep throat culture, however. In these cases, serial strep titers may give evidence of a subclinical infection. If strep is present, children should take a full course of antibiotics and return for a repeat culture shortly after the antibiotic is completed.

PANDAS appears to be at the center of a convergence of three factors, Dr. Murphy said: a group A strep infection, genetic predisposition (familial OCD, Tourette's syndrome, or rheumatoid fever, including Sydenham's chorea), and an environmental stress factor such as a central nervous system injury or coinfection. The incidence peaks at ages 5–12 years–the same ages in which strep infections peak.

Dr. Murphy presented the results of a prospective study of 25 children, aged 7–17 years, with typical OCD and tics. The children were assessed every 6 weeks and had at least 6 consecutive assessments; strep titers were taken at each visit. Fifteen children exhibited an episodic or sawtooth disease course. Almost 60% of the episodic group had elevated group A strep titers on all of their visits, while 60% of the steady disease course group had no elevated titers at any time, suggesting that those with a PANDAS-like course have had more frequent undetected strep infections or prolonged immune reaction to past strep infections.

Those with episodic disease were also more likely to have exacerbations in the fall and winter, concurrent with the seasonal rise in strep infections. The children in the episodic group were more likely to be male (67% vs. 30%) and have attention-deficit hyperactivity disorder (73% vs. 40%), compared with those in the steady course group.

“Unlike its namesake, however, PANDAS isn't all black and white,” Dr. Murphy said. There have been few reports that antibiotics for children suspected of having the disorder improved their OCD or tic symptoms. Definitive studies still need to be conducted to clarify the impact of antibiotic treatment on symptoms.

In a 2005 study, 23 children with PANDAS received either azithromycin or penicillin prophylaxis. The drugs decreased additional strep infections and neuropsychiatric symptom exacerbations (Biol. Psychiatry 2005;57:788–92).

In 2002, a prospective study found that children with PANDAS experienced OCD symptom resolution after receiving antibiotics at the sentinel OCD episode (Arch. Pediatr. Adolesc. Med. 2002;156:356–61).

An early clinical trial involving the use of prophylactic penicillin for PANDAS revealed no conclusive evidence that the antibiotic reduced clinical exacerbation. However, the sample size was small (37 subjects), the treatment arm was brief, and the lack of efficacy may have been attributable to the failure of antibiotic therapy to eliminate streptococcal colonization in the patients enrolled in the study, Dr. Murphy said. Since then, investigators have reported improvement in neuropsychiatric symptoms with antibiotic treatment in patients presenting with PANDAS. Difficulties with study design and the small sample size of these early antibiotic trials limit the clinical influence of their findings.