Sharon Worcester

Magnetic resonance imaging of the brain helped to determine the duration of a stroke in patients with unknown onset time, and thereby improved the ability to identify patients who were eligible for thrombolysis in a small retrospective study.

The study, published online in the Nov. 2 issue of Radiology, is an early look at ways of using MRI to manage all stroke patients urgently, "not just those patients with a known onset of symptoms," Dr. Catherine Oppenheim, lead investigator, said in a statement from the Radiological Society of North America, which publishes Radiology.

The study included 77 men and 53 women with a mean age of 65 years who presented consecutively between May 2006 and October 2008 with acute ischemic stroke with known onset time. They underwent 1.5-T MR imaging within 12 hours of symptom onset.

Imaging ratios in 63 patients who underwent imaging within 3 hours of symptom onset differed significantly from those in 67 patients who underwent imaging more than 3 hours after symptom onset, allowing first author Dr. Mina Petkova of Université Paris (France) Descartes and colleagues to identify which patients were within the 3-hour window that deemed them eligible for thrombolysis with tissue plasminogen activator (tPA).

Only 13 of those patients were imaged 3-4.5 hours after onset. (Since the fall of 2008, the American Heart Association, the American Stroke Association, and the European Stroke Organization have recommended that the tPA treatment time window be expanded to within 4.5 hours after stroke onset.)

Specifically, the fluid-attenuated inversion recovery (FLAIR) ratio showed a positive correlation with time from symptom onset, and the investigators demonstrated that this ratio could identify patients imaged within 3 hours of symptom onset with 90% sensitivity and 92% specificity when a 7% FLAIR ratio cutoff was used. Additionally, visual inspection of FLAIR and diffusion-weighted (DW) images was able to identify stroke imaged within 3 hours with 94% sensitivity and 97% specificity, the investigators found (Radiology 2010 Nov. 2 [doi:10.1148/radiol.10100461]).

The findings based on both these quantitative and qualitative analyses could have implications for the approximately 25% of stroke patients who don’t know, or who are unable to communicate, when their stroke symptoms began, according to Dr. Oppenheim, professor of radiology at the university.

That is, brain MRI could be used as a surrogate marker of stroke age in cases when the time of stroke onset is unknown or uncertain to help identify those who are within "the time window for which intravenous thrombolysis has proved effective, is approved, and is recommended by international guidelines," the investigators wrote.

One implication of the finding that 1.5-T MR imaging provides reliable stroke age estimation is a potential increase in the number of patients eligible for thrombolysis.

"Our results confirm that further, prospective multicenter studies in which the safety of thrombolysis is assessed in patients with unknown stroke onset time should integrate, among other things, parameters used to estimate stroke age on the basis of FLAIR imaging," the investigators concluded.

The investigators had no financial relationship to disclose.

Magnetic resonance imaging of the brain helped to determine the duration of a stroke in patients with unknown onset time, and thereby improved the ability to identify patients who were eligible for thrombolysis in a small retrospective study.

The study, published online in the Nov. 2 issue of Radiology, is an early look at ways of using MRI to manage all stroke patients urgently, "not just those patients with a known onset of symptoms," Dr. Catherine Oppenheim, lead investigator, said in a statement from the Radiological Society of North America, which publishes Radiology.

The study included 77 men and 53 women with a mean age of 65 years who presented consecutively between May 2006 and October 2008 with acute ischemic stroke with known onset time. They underwent 1.5-T MR imaging within 12 hours of symptom onset.

Imaging ratios in 63 patients who underwent imaging within 3 hours of symptom onset differed significantly from those in 67 patients who underwent imaging more than 3 hours after symptom onset, allowing first author Dr. Mina Petkova of Université Paris (France) Descartes and colleagues to identify which patients were within the 3-hour window that deemed them eligible for thrombolysis with tissue plasminogen activator (tPA).

Only 13 of those patients were imaged 3-4.5 hours after onset. (Since the fall of 2008, the American Heart Association, the American Stroke Association, and the European Stroke Organization have recommended that the tPA treatment time window be expanded to within 4.5 hours after stroke onset.)

Specifically, the fluid-attenuated inversion recovery (FLAIR) ratio showed a positive correlation with time from symptom onset, and the investigators demonstrated that this ratio could identify patients imaged within 3 hours of symptom onset with 90% sensitivity and 92% specificity when a 7% FLAIR ratio cutoff was used. Additionally, visual inspection of FLAIR and diffusion-weighted (DW) images was able to identify stroke imaged within 3 hours with 94% sensitivity and 97% specificity, the investigators found (Radiology 2010 Nov. 2 [doi:10.1148/radiol.10100461]).

The findings based on both these quantitative and qualitative analyses could have implications for the approximately 25% of stroke patients who don’t know, or who are unable to communicate, when their stroke symptoms began, according to Dr. Oppenheim, professor of radiology at the university.

That is, brain MRI could be used as a surrogate marker of stroke age in cases when the time of stroke onset is unknown or uncertain to help identify those who are within "the time window for which intravenous thrombolysis has proved effective, is approved, and is recommended by international guidelines," the investigators wrote.

One implication of the finding that 1.5-T MR imaging provides reliable stroke age estimation is a potential increase in the number of patients eligible for thrombolysis.

"Our results confirm that further, prospective multicenter studies in which the safety of thrombolysis is assessed in patients with unknown stroke onset time should integrate, among other things, parameters used to estimate stroke age on the basis of FLAIR imaging," the investigators concluded.

The investigators had no financial relationship to disclose.

Magnetic resonance imaging of the brain helped to determine the duration of a stroke in patients with unknown onset time, and thereby improved the ability to identify patients who were eligible for thrombolysis in a small retrospective study.

The study, published online in the Nov. 2 issue of Radiology, is an early look at ways of using MRI to manage all stroke patients urgently, "not just those patients with a known onset of symptoms," Dr. Catherine Oppenheim, lead investigator, said in a statement from the Radiological Society of North America, which publishes Radiology.

The study included 77 men and 53 women with a mean age of 65 years who presented consecutively between May 2006 and October 2008 with acute ischemic stroke with known onset time. They underwent 1.5-T MR imaging within 12 hours of symptom onset.

Imaging ratios in 63 patients who underwent imaging within 3 hours of symptom onset differed significantly from those in 67 patients who underwent imaging more than 3 hours after symptom onset, allowing first author Dr. Mina Petkova of Université Paris (France) Descartes and colleagues to identify which patients were within the 3-hour window that deemed them eligible for thrombolysis with tissue plasminogen activator (tPA).

Only 13 of those patients were imaged 3-4.5 hours after onset. (Since the fall of 2008, the American Heart Association, the American Stroke Association, and the European Stroke Organization have recommended that the tPA treatment time window be expanded to within 4.5 hours after stroke onset.)

Specifically, the fluid-attenuated inversion recovery (FLAIR) ratio showed a positive correlation with time from symptom onset, and the investigators demonstrated that this ratio could identify patients imaged within 3 hours of symptom onset with 90% sensitivity and 92% specificity when a 7% FLAIR ratio cutoff was used. Additionally, visual inspection of FLAIR and diffusion-weighted (DW) images was able to identify stroke imaged within 3 hours with 94% sensitivity and 97% specificity, the investigators found (Radiology 2010 Nov. 2 [doi:10.1148/radiol.10100461]).

The findings based on both these quantitative and qualitative analyses could have implications for the approximately 25% of stroke patients who don’t know, or who are unable to communicate, when their stroke symptoms began, according to Dr. Oppenheim, professor of radiology at the university.

That is, brain MRI could be used as a surrogate marker of stroke age in cases when the time of stroke onset is unknown or uncertain to help identify those who are within "the time window for which intravenous thrombolysis has proved effective, is approved, and is recommended by international guidelines," the investigators wrote.

One implication of the finding that 1.5-T MR imaging provides reliable stroke age estimation is a potential increase in the number of patients eligible for thrombolysis.

"Our results confirm that further, prospective multicenter studies in which the safety of thrombolysis is assessed in patients with unknown stroke onset time should integrate, among other things, parameters used to estimate stroke age on the basis of FLAIR imaging," the investigators concluded.

The investigators had no financial relationship to disclose.

Magnetic resonance imaging of the brain helped to determine the duration of a stroke in patients with unknown onset time, and thereby improved the ability to identify patients who were eligible for thrombolysis in a small retrospective study.

The study, published online in the Nov. 2 issue of Radiology, is an early look at ways of using MRI to manage all stroke patients urgently, "not just those patients with a known onset of symptoms," Dr. Catherine Oppenheim, lead investigator, said in a statement from the Radiological Society of North America, which publishes Radiology.

The study included 77 men and 53 women with a mean age of 65 years who presented consecutively between May 2006 and October 2008 with acute ischemic stroke with known onset time. They underwent 1.5-T MR imaging within 12 hours of symptom onset.

Imaging ratios in 63 patients who underwent imaging within 3 hours of symptom onset differed significantly from those in 67 patients who underwent imaging more than 3 hours after symptom onset, allowing first author Dr. Mina Petkova of Université Paris (France) Descartes and colleagues to identify which patients were within the 3-hour window that deemed them eligible for thrombolysis with tissue plasminogen activator (tPA).

Only 13 of those patients were imaged 3-4.5 hours after onset. (Since the fall of 2008, the American Heart Association, the American Stroke Association, and the European Stroke Organization have recommended that the tPA treatment time window be expanded to within 4.5 hours after stroke onset.)

Specifically, the fluid-attenuated inversion recovery (FLAIR) ratio showed a positive correlation with time from symptom onset, and the investigators demonstrated that this ratio could identify patients imaged within 3 hours of symptom onset with 90% sensitivity and 92% specificity when a 7% FLAIR ratio cutoff was used. Additionally, visual inspection of FLAIR and diffusion-weighted (DW) images was able to identify stroke imaged within 3 hours with 94% sensitivity and 97% specificity, the investigators found (Radiology 2010 Nov. 2 [doi:10.1148/radiol.10100461]).

The findings based on both these quantitative and qualitative analyses could have implications for the approximately 25% of stroke patients who don’t know, or who are unable to communicate, when their stroke symptoms began, according to Dr. Oppenheim, professor of radiology at the university.

That is, brain MRI could be used as a surrogate marker of stroke age in cases when the time of stroke onset is unknown or uncertain to help identify those who are within "the time window for which intravenous thrombolysis has proved effective, is approved, and is recommended by international guidelines," the investigators wrote.

One implication of the finding that 1.5-T MR imaging provides reliable stroke age estimation is a potential increase in the number of patients eligible for thrombolysis.

"Our results confirm that further, prospective multicenter studies in which the safety of thrombolysis is assessed in patients with unknown stroke onset time should integrate, among other things, parameters used to estimate stroke age on the basis of FLAIR imaging," the investigators concluded.

The investigators had no financial relationship to disclose.

Magnetic resonance imaging of the brain helped to determine the duration of a stroke in patients with unknown onset time, and thereby improved the ability to identify patients who were eligible for thrombolysis in a small retrospective study.

The study, published online in the Nov. 2 issue of Radiology, is an early look at ways of using MRI to manage all stroke patients urgently, "not just those patients with a known onset of symptoms," Dr. Catherine Oppenheim, lead investigator, said in a statement from the Radiological Society of North America, which publishes Radiology.

The study included 77 men and 53 women with a mean age of 65 years who presented consecutively between May 2006 and October 2008 with acute ischemic stroke with known onset time. They underwent 1.5-T MR imaging within 12 hours of symptom onset.

Imaging ratios in 63 patients who underwent imaging within 3 hours of symptom onset differed significantly from those in 67 patients who underwent imaging more than 3 hours after symptom onset, allowing first author Dr. Mina Petkova of Université Paris (France) Descartes and colleagues to identify which patients were within the 3-hour window that deemed them eligible for thrombolysis with tissue plasminogen activator (tPA).

Only 13 of those patients were imaged 3-4.5 hours after onset. (Since the fall of 2008, the American Heart Association, the American Stroke Association, and the European Stroke Organization have recommended that the tPA treatment time window be expanded to within 4.5 hours after stroke onset.)

Specifically, the fluid-attenuated inversion recovery (FLAIR) ratio showed a positive correlation with time from symptom onset, and the investigators demonstrated that this ratio could identify patients imaged within 3 hours of symptom onset with 90% sensitivity and 92% specificity when a 7% FLAIR ratio cutoff was used. Additionally, visual inspection of FLAIR and diffusion-weighted (DW) images was able to identify stroke imaged within 3 hours with 94% sensitivity and 97% specificity, the investigators found (Radiology 2010 Nov. 2 [doi:10.1148/radiol.10100461]).

The findings based on both these quantitative and qualitative analyses could have implications for the approximately 25% of stroke patients who don’t know, or who are unable to communicate, when their stroke symptoms began, according to Dr. Oppenheim, professor of radiology at the university.

That is, brain MRI could be used as a surrogate marker of stroke age in cases when the time of stroke onset is unknown or uncertain to help identify those who are within "the time window for which intravenous thrombolysis has proved effective, is approved, and is recommended by international guidelines," the investigators wrote.

One implication of the finding that 1.5-T MR imaging provides reliable stroke age estimation is a potential increase in the number of patients eligible for thrombolysis.

"Our results confirm that further, prospective multicenter studies in which the safety of thrombolysis is assessed in patients with unknown stroke onset time should integrate, among other things, parameters used to estimate stroke age on the basis of FLAIR imaging," the investigators concluded.

The investigators had no financial relationship to disclose.

Magnetic resonance imaging of the brain helped to determine the duration of a stroke in patients with unknown onset time, and thereby improved the ability to identify patients who were eligible for thrombolysis in a small retrospective study.

The study, published online in the Nov. 2 issue of Radiology, is an early look at ways of using MRI to manage all stroke patients urgently, "not just those patients with a known onset of symptoms," Dr. Catherine Oppenheim, lead investigator, said in a statement from the Radiological Society of North America, which publishes Radiology.

The study included 77 men and 53 women with a mean age of 65 years who presented consecutively between May 2006 and October 2008 with acute ischemic stroke with known onset time. They underwent 1.5-T MR imaging within 12 hours of symptom onset.

Imaging ratios in 63 patients who underwent imaging within 3 hours of symptom onset differed significantly from those in 67 patients who underwent imaging more than 3 hours after symptom onset, allowing first author Dr. Mina Petkova of Université Paris (France) Descartes and colleagues to identify which patients were within the 3-hour window that deemed them eligible for thrombolysis with tissue plasminogen activator (tPA).

Only 13 of those patients were imaged 3-4.5 hours after onset. (Since the fall of 2008, the American Heart Association, the American Stroke Association, and the European Stroke Organization have recommended that the tPA treatment time window be expanded to within 4.5 hours after stroke onset.)

Specifically, the fluid-attenuated inversion recovery (FLAIR) ratio showed a positive correlation with time from symptom onset, and the investigators demonstrated that this ratio could identify patients imaged within 3 hours of symptom onset with 90% sensitivity and 92% specificity when a 7% FLAIR ratio cutoff was used. Additionally, visual inspection of FLAIR and diffusion-weighted (DW) images was able to identify stroke imaged within 3 hours with 94% sensitivity and 97% specificity, the investigators found (Radiology 2010 Nov. 2 [doi:10.1148/radiol.10100461]).

The findings based on both these quantitative and qualitative analyses could have implications for the approximately 25% of stroke patients who don’t know, or who are unable to communicate, when their stroke symptoms began, according to Dr. Oppenheim, professor of radiology at the university.

That is, brain MRI could be used as a surrogate marker of stroke age in cases when the time of stroke onset is unknown or uncertain to help identify those who are within "the time window for which intravenous thrombolysis has proved effective, is approved, and is recommended by international guidelines," the investigators wrote.

One implication of the finding that 1.5-T MR imaging provides reliable stroke age estimation is a potential increase in the number of patients eligible for thrombolysis.

"Our results confirm that further, prospective multicenter studies in which the safety of thrombolysis is assessed in patients with unknown stroke onset time should integrate, among other things, parameters used to estimate stroke age on the basis of FLAIR imaging," the investigators concluded.

The investigators had no financial relationship to disclose.

ST. LOUIS — Complaints of vaginal discharge, bleeding, and/or general vaginal discomfort in a patient who has undergone sling placement may signal vaginal mesh erosion.

Patients with vaginal mesh erosion might also note that their partner “feels something” in the vagina during intercourse, Dr. Ginger Cathey said at the conference, which was sponsored by the Society of Pelvic Reconstructive Surgeons.

Vaginal mesh erosion occurs in about 0.5% of synthetic sling patients, according to the most recent reports in the literature, and in most cases, the mesh erosion will be quite apparent although, in some cases, the mesh fibers can be felt, but not visualized, said Dr. Cathey, a practicing urogynecologist at Baylor College of Medicine, Houston.

Bladder and urethral mesh erosions are far less common, with only case reports appearing in the literature. Patients with bladder or urethral erosions might present with complaints of recurrent urinary tract infections, irritative voiding symptoms such as frequency and urgency, and hematuria. Consider these types of erosions if you have a sling-placement patient who complains of greater frequency and urgency than before the procedure and who has normal post void residuals, Dr. Cathey advised.

Management of vaginal mesh erosion – which usually occurs in the midurethral area, can include local estrogen, especially in cases where a few fibers can be palpated, but not seen, or when the patient is hesitant about excision. However, Dr. Cathey has doubts about the ability of local estrogen to promote re-epithelialization. Excision, she said, is her preferred approach to management of vaginal mesh erosion, and it can generally be performed in the office. “It's very rare that I would take a sling erosion back to the operating room to excise it,” she said. Even if a patient has undergone excision and comes back saying they still feel something, you may be able to remove the remaining fibers in the office by using a colposcope and a suture removal kit to tweeze out the fibers and snip them at that time.

Treatment of larger areas involving exposed tissues or recurrent erosion is best treated by advancing the vaginal epithelium to cover the defect, Dr. Cathey said, noting that use of a Martius graft in such cases would be overkill, but that such a graft would be reasonable in cases of urethral erosion in which the patient has developed a urethral-vaginal fistula.

For bladder or urethral erosion, avoid urethral dilation, which can loosen the sling, but which also places the sling closer to the urethra thereby increasing the potential for more erosion, Dr. Cathey explained.

Try to manage these patients “as minimally invasively as possible,” she said.

Separation of the mesh from the bladder can be challenging, but it can be accomplished using laparoscopic or cystoscopic equipment, or by mini-laparotomy, she noted.

“If you want to resect all the mesh fibers, it's really important that you put counter-traction on the mesh before cutting it,” she said, noting that the simplest approach is to distend the bladder and to place a 5-mm suprapubic trocar through the bladder, using it to apply traction while you take the endoscopic endoshears and trim the mesh as closely as possible.

If a patient treated for bladder or urethral erosion presents with recurrent irritating voiding symptoms, be sure to evaluate the contralateral side for a second erosion, she said.

Dr. Cathey disclosed that she is a consultant for Bard Medical.

ST. LOUIS — Complaints of vaginal discharge, bleeding, and/or general vaginal discomfort in a patient who has undergone sling placement may signal vaginal mesh erosion.

Patients with vaginal mesh erosion might also note that their partner “feels something” in the vagina during intercourse, Dr. Ginger Cathey said at the conference, which was sponsored by the Society of Pelvic Reconstructive Surgeons.

Vaginal mesh erosion occurs in about 0.5% of synthetic sling patients, according to the most recent reports in the literature, and in most cases, the mesh erosion will be quite apparent although, in some cases, the mesh fibers can be felt, but not visualized, said Dr. Cathey, a practicing urogynecologist at Baylor College of Medicine, Houston.

Bladder and urethral mesh erosions are far less common, with only case reports appearing in the literature. Patients with bladder or urethral erosions might present with complaints of recurrent urinary tract infections, irritative voiding symptoms such as frequency and urgency, and hematuria. Consider these types of erosions if you have a sling-placement patient who complains of greater frequency and urgency than before the procedure and who has normal post void residuals, Dr. Cathey advised.

Management of vaginal mesh erosion – which usually occurs in the midurethral area, can include local estrogen, especially in cases where a few fibers can be palpated, but not seen, or when the patient is hesitant about excision. However, Dr. Cathey has doubts about the ability of local estrogen to promote re-epithelialization. Excision, she said, is her preferred approach to management of vaginal mesh erosion, and it can generally be performed in the office. “It's very rare that I would take a sling erosion back to the operating room to excise it,” she said. Even if a patient has undergone excision and comes back saying they still feel something, you may be able to remove the remaining fibers in the office by using a colposcope and a suture removal kit to tweeze out the fibers and snip them at that time.

Treatment of larger areas involving exposed tissues or recurrent erosion is best treated by advancing the vaginal epithelium to cover the defect, Dr. Cathey said, noting that use of a Martius graft in such cases would be overkill, but that such a graft would be reasonable in cases of urethral erosion in which the patient has developed a urethral-vaginal fistula.

For bladder or urethral erosion, avoid urethral dilation, which can loosen the sling, but which also places the sling closer to the urethra thereby increasing the potential for more erosion, Dr. Cathey explained.

Try to manage these patients “as minimally invasively as possible,” she said.

Separation of the mesh from the bladder can be challenging, but it can be accomplished using laparoscopic or cystoscopic equipment, or by mini-laparotomy, she noted.

“If you want to resect all the mesh fibers, it's really important that you put counter-traction on the mesh before cutting it,” she said, noting that the simplest approach is to distend the bladder and to place a 5-mm suprapubic trocar through the bladder, using it to apply traction while you take the endoscopic endoshears and trim the mesh as closely as possible.

If a patient treated for bladder or urethral erosion presents with recurrent irritating voiding symptoms, be sure to evaluate the contralateral side for a second erosion, she said.

Dr. Cathey disclosed that she is a consultant for Bard Medical.

ST. LOUIS — Complaints of vaginal discharge, bleeding, and/or general vaginal discomfort in a patient who has undergone sling placement may signal vaginal mesh erosion.

Patients with vaginal mesh erosion might also note that their partner “feels something” in the vagina during intercourse, Dr. Ginger Cathey said at the conference, which was sponsored by the Society of Pelvic Reconstructive Surgeons.

Vaginal mesh erosion occurs in about 0.5% of synthetic sling patients, according to the most recent reports in the literature, and in most cases, the mesh erosion will be quite apparent although, in some cases, the mesh fibers can be felt, but not visualized, said Dr. Cathey, a practicing urogynecologist at Baylor College of Medicine, Houston.

Bladder and urethral mesh erosions are far less common, with only case reports appearing in the literature. Patients with bladder or urethral erosions might present with complaints of recurrent urinary tract infections, irritative voiding symptoms such as frequency and urgency, and hematuria. Consider these types of erosions if you have a sling-placement patient who complains of greater frequency and urgency than before the procedure and who has normal post void residuals, Dr. Cathey advised.

Management of vaginal mesh erosion – which usually occurs in the midurethral area, can include local estrogen, especially in cases where a few fibers can be palpated, but not seen, or when the patient is hesitant about excision. However, Dr. Cathey has doubts about the ability of local estrogen to promote re-epithelialization. Excision, she said, is her preferred approach to management of vaginal mesh erosion, and it can generally be performed in the office. “It's very rare that I would take a sling erosion back to the operating room to excise it,” she said. Even if a patient has undergone excision and comes back saying they still feel something, you may be able to remove the remaining fibers in the office by using a colposcope and a suture removal kit to tweeze out the fibers and snip them at that time.

Treatment of larger areas involving exposed tissues or recurrent erosion is best treated by advancing the vaginal epithelium to cover the defect, Dr. Cathey said, noting that use of a Martius graft in such cases would be overkill, but that such a graft would be reasonable in cases of urethral erosion in which the patient has developed a urethral-vaginal fistula.

For bladder or urethral erosion, avoid urethral dilation, which can loosen the sling, but which also places the sling closer to the urethra thereby increasing the potential for more erosion, Dr. Cathey explained.

Try to manage these patients “as minimally invasively as possible,” she said.

Separation of the mesh from the bladder can be challenging, but it can be accomplished using laparoscopic or cystoscopic equipment, or by mini-laparotomy, she noted.

“If you want to resect all the mesh fibers, it's really important that you put counter-traction on the mesh before cutting it,” she said, noting that the simplest approach is to distend the bladder and to place a 5-mm suprapubic trocar through the bladder, using it to apply traction while you take the endoscopic endoshears and trim the mesh as closely as possible.

If a patient treated for bladder or urethral erosion presents with recurrent irritating voiding symptoms, be sure to evaluate the contralateral side for a second erosion, she said.

Dr. Cathey disclosed that she is a consultant for Bard Medical.

ST. LOUIS — Coring is an excellent technique for facilitating vaginal hysterectomy in patients with large adenomyotic uteri, according to Dr. Carl W. Zimmerman.

Adenomyosis creates a very dense, unforgiving myometrium that is very symptomatic for the patient, and affected uteri can reach at least 20 weeks in size without a well-defined mass that can be enucleated, he said at the conference, which was sponsored by the Society of Pelvic Reconstructive Surgeons.

Debulking is a challenge in cases like this, but a coring technique that changes the shape of the uterus can ease removal.

An incision is made around the cervix, the paracolpium is divided, and the blood supply is divided, creating a bloodless organ, he said.

“What you do then is take a knife and make an encircling cut concentrically around the cervix and into the fundus of the uterus, but parallel to the long access of the uterus and endometrial cavity, going around and around and around,” explained Dr. Zimmerman, professor of obstetrics and gynecology at Vanderbilt University, Nashville, Tenn.

If you do this long enough, and make incisions parallel to the endometrial cavity and away from the serosal surface of the uterus, the globular structure is converted to a tubular structure that can be a foot long or longer, and which “literally comes down to meet you,” he said.

Dr. Zimmerman is a speaker/proctor for Cook Medical, is a proctor for Boston Scientific Corp. and Covidien, and receives royalties from Lumitex Inc. and Marina Medical Instruments Inc.

ST. LOUIS — Coring is an excellent technique for facilitating vaginal hysterectomy in patients with large adenomyotic uteri, according to Dr. Carl W. Zimmerman.

Adenomyosis creates a very dense, unforgiving myometrium that is very symptomatic for the patient, and affected uteri can reach at least 20 weeks in size without a well-defined mass that can be enucleated, he said at the conference, which was sponsored by the Society of Pelvic Reconstructive Surgeons.

Debulking is a challenge in cases like this, but a coring technique that changes the shape of the uterus can ease removal.

An incision is made around the cervix, the paracolpium is divided, and the blood supply is divided, creating a bloodless organ, he said.

“What you do then is take a knife and make an encircling cut concentrically around the cervix and into the fundus of the uterus, but parallel to the long access of the uterus and endometrial cavity, going around and around and around,” explained Dr. Zimmerman, professor of obstetrics and gynecology at Vanderbilt University, Nashville, Tenn.

If you do this long enough, and make incisions parallel to the endometrial cavity and away from the serosal surface of the uterus, the globular structure is converted to a tubular structure that can be a foot long or longer, and which “literally comes down to meet you,” he said.

Dr. Zimmerman is a speaker/proctor for Cook Medical, is a proctor for Boston Scientific Corp. and Covidien, and receives royalties from Lumitex Inc. and Marina Medical Instruments Inc.

ST. LOUIS — Coring is an excellent technique for facilitating vaginal hysterectomy in patients with large adenomyotic uteri, according to Dr. Carl W. Zimmerman.

Adenomyosis creates a very dense, unforgiving myometrium that is very symptomatic for the patient, and affected uteri can reach at least 20 weeks in size without a well-defined mass that can be enucleated, he said at the conference, which was sponsored by the Society of Pelvic Reconstructive Surgeons.

Debulking is a challenge in cases like this, but a coring technique that changes the shape of the uterus can ease removal.

An incision is made around the cervix, the paracolpium is divided, and the blood supply is divided, creating a bloodless organ, he said.

“What you do then is take a knife and make an encircling cut concentrically around the cervix and into the fundus of the uterus, but parallel to the long access of the uterus and endometrial cavity, going around and around and around,” explained Dr. Zimmerman, professor of obstetrics and gynecology at Vanderbilt University, Nashville, Tenn.

If you do this long enough, and make incisions parallel to the endometrial cavity and away from the serosal surface of the uterus, the globular structure is converted to a tubular structure that can be a foot long or longer, and which “literally comes down to meet you,” he said.

Dr. Zimmerman is a speaker/proctor for Cook Medical, is a proctor for Boston Scientific Corp. and Covidien, and receives royalties from Lumitex Inc. and Marina Medical Instruments Inc.

ST. LOUIS — The vast majority of benign hysterectomies can – and should – be performed vaginally, according to Dr. Carl W. Zimmerman.

In fact, more than 90% of uteri weighing less than 250 g are accessible and can safely be removed vaginally by using guidelines endorsed by the board of directors of the Society of Pelvic Reconstructive Surgeons. Considerable evidence exists that many larger uteri also can be removed safely via the vaginal route, he said at the conference, which was sponsored by the society.

Despite this evidence, however, the minimally invasive vaginal approach remains underused in the United States, said Dr. Zimmerman, professor of obstetrics and gynecology at Vanderbilt University, Nashville, Tenn.

A lack of experience, familiarity with technique, and confidence is the main reasons why surgeons avoid the vaginal approach in favor of more invasive abdominal, laparoscopic, and robotic techniques. While the choice for vaginal hysterectomy should be made based – to a certain extent – on guidelines, it is important to consider skill acquisition, experience and competency, he said.

He encouraged those who are “on a learning curve” in terms of performing vaginal hysterectomy in patients with large uteri to obtain more experience by using this technique for uteri of 14–16 week size.

“That may sound big, but you'll be amazed, you'll be empowered, and your patients will do well,” he said, strongly recommending consideration of the concept of removing larger uteri by this method.

He outlined five main steps that must be completed to successfully remove an enlarged uterus vaginally, and provided tips on surgical instrumentation that can facilitate vaginal hysterectomy in cases involving a large uterus.

The first step is entry into the peritoneal cavity. This can be accomplished anteriorly or posteriorly, but experienced operators will delay entry into the anterior segment until the uterosacral and cardinal ligaments have been detached, and therefore they typically enter posteriorly.

“It's often available to you, and it's the easiest entry into the peritoneal cavity,” he said of the posterior approach.

The next two steps are to detach the uterosacral and cardinal ligaments, and to ligate the uterine artery.

Keep in mind that fibroids are the most common cause of uterine enlargement, and that most of the anatomical distortions in the fibroid uterus are limited to the area superior to the uterine artery. This “concept of uterine anatomic distortion” means that once steps 1–3 are completed, you “can be innovative about the way you debulk and remove the uterus. Once you have secured the support system, and you have divided the blood supply, then it becomes a mechanical exercise in converting a roughly globular structure into either various components that will come out, or a shape that will change and come out,” he explained.

Once the fourth step of debulking and removing the uterus is completed, the final step – vaginal adnexectomy – can be performed as needed based on the same indications that would be used if a scope was in place, or if the procedure was done abdominally, he said.

As for the best approaches to debulking the uterus, Dr. Zimmerman said morcellation is his primary technique, followed by coring, which is very useful for the adenomyotic uterus – and is particularly valuable for managing uteri up to 17 weeks in size.

The typical tools used in gynecologic surgery, such as Haney clamps, straight needle holders, and short instruments may be inadequate for performing vaginal hysterectomy involving large uteri. Instruments Dr. Zimmerman recommends for improving surgical skill and outcome include:

▸ Retractors. The correct retractors are one of the keys to success in vaginal hysterectomy; shop around and find the type that fits best into your system, Dr. Zimmerman advised. He listed Heaney, Harrington, malleable ribbon, Breisky-Navratil, and Steiner-Auvard among good options. Deaver retractors should be avoided because they increase risk of bladder injury, he said.

▸ Scissors. The right scissors can help with debulking when difficult angles are encountered. Jorgenson scissors, which Dr. Zimmerman learned to use in abdominal hysterectomy, are also useful in vaginal hysterectomy, because they create a right angle very valuable for debulking the uterus. Martin cartilage scissors, which have sharp points at the tips that can allow for insertion into a myoma and allow wedges to be cut, are very helpful, he said. Even a very dense or calcified myoma can be transected and debulked using these scissors.

▸ Lights. Whatever you choose to use to gain extra light is a good idea, he added. The Vital Vue surgical light, and a newer version – the Versalight, which is a multifunctional surgical light that provides irrigation, suction, and retraction, are good options. Dr. Zimmerman disclosed that he helped design the Versalight.

▸ Vulsellum forceps. These are useful for grasping myoma. Lahey, Gordon, and Segond forceps are all good options.

▸ Myotomes. Cobb and Langenbeck periosteal elevators that have been modified into both chisel tip and spoon tip myotomes can be helpful for enucleation.

With the proper equipment and surgical skills, vaginal hysterectomy is feasible in most cases, and the reduced morbidity, costs, and hospital length of stay associated with this approach should be enough incentive to encourage gynecologists to increase proficiency in the vaginal approach, Dr. Zimmerman said.

Keep in mind, he added, that in appropriately informed patients who have given consent to surgery, conversion to a more invasive approach is not a complication.

Dr. Zimmerman is a speaker/proctor for Cook Medical, proctor for Boston Scientific Corp. and Covidien, and receives Royalties from Lumitex Inc. and Marina Medical Instruments Inc.

ST. LOUIS — The vast majority of benign hysterectomies can – and should – be performed vaginally, according to Dr. Carl W. Zimmerman.

In fact, more than 90% of uteri weighing less than 250 g are accessible and can safely be removed vaginally by using guidelines endorsed by the board of directors of the Society of Pelvic Reconstructive Surgeons. Considerable evidence exists that many larger uteri also can be removed safely via the vaginal route, he said at the conference, which was sponsored by the society.

Despite this evidence, however, the minimally invasive vaginal approach remains underused in the United States, said Dr. Zimmerman, professor of obstetrics and gynecology at Vanderbilt University, Nashville, Tenn.

A lack of experience, familiarity with technique, and confidence is the main reasons why surgeons avoid the vaginal approach in favor of more invasive abdominal, laparoscopic, and robotic techniques. While the choice for vaginal hysterectomy should be made based – to a certain extent – on guidelines, it is important to consider skill acquisition, experience and competency, he said.

He encouraged those who are “on a learning curve” in terms of performing vaginal hysterectomy in patients with large uteri to obtain more experience by using this technique for uteri of 14–16 week size.

“That may sound big, but you'll be amazed, you'll be empowered, and your patients will do well,” he said, strongly recommending consideration of the concept of removing larger uteri by this method.

He outlined five main steps that must be completed to successfully remove an enlarged uterus vaginally, and provided tips on surgical instrumentation that can facilitate vaginal hysterectomy in cases involving a large uterus.

The first step is entry into the peritoneal cavity. This can be accomplished anteriorly or posteriorly, but experienced operators will delay entry into the anterior segment until the uterosacral and cardinal ligaments have been detached, and therefore they typically enter posteriorly.

“It's often available to you, and it's the easiest entry into the peritoneal cavity,” he said of the posterior approach.

The next two steps are to detach the uterosacral and cardinal ligaments, and to ligate the uterine artery.

Keep in mind that fibroids are the most common cause of uterine enlargement, and that most of the anatomical distortions in the fibroid uterus are limited to the area superior to the uterine artery. This “concept of uterine anatomic distortion” means that once steps 1–3 are completed, you “can be innovative about the way you debulk and remove the uterus. Once you have secured the support system, and you have divided the blood supply, then it becomes a mechanical exercise in converting a roughly globular structure into either various components that will come out, or a shape that will change and come out,” he explained.

Once the fourth step of debulking and removing the uterus is completed, the final step – vaginal adnexectomy – can be performed as needed based on the same indications that would be used if a scope was in place, or if the procedure was done abdominally, he said.

As for the best approaches to debulking the uterus, Dr. Zimmerman said morcellation is his primary technique, followed by coring, which is very useful for the adenomyotic uterus – and is particularly valuable for managing uteri up to 17 weeks in size.

The typical tools used in gynecologic surgery, such as Haney clamps, straight needle holders, and short instruments may be inadequate for performing vaginal hysterectomy involving large uteri. Instruments Dr. Zimmerman recommends for improving surgical skill and outcome include:

▸ Retractors. The correct retractors are one of the keys to success in vaginal hysterectomy; shop around and find the type that fits best into your system, Dr. Zimmerman advised. He listed Heaney, Harrington, malleable ribbon, Breisky-Navratil, and Steiner-Auvard among good options. Deaver retractors should be avoided because they increase risk of bladder injury, he said.

▸ Scissors. The right scissors can help with debulking when difficult angles are encountered. Jorgenson scissors, which Dr. Zimmerman learned to use in abdominal hysterectomy, are also useful in vaginal hysterectomy, because they create a right angle very valuable for debulking the uterus. Martin cartilage scissors, which have sharp points at the tips that can allow for insertion into a myoma and allow wedges to be cut, are very helpful, he said. Even a very dense or calcified myoma can be transected and debulked using these scissors.

▸ Lights. Whatever you choose to use to gain extra light is a good idea, he added. The Vital Vue surgical light, and a newer version – the Versalight, which is a multifunctional surgical light that provides irrigation, suction, and retraction, are good options. Dr. Zimmerman disclosed that he helped design the Versalight.

▸ Vulsellum forceps. These are useful for grasping myoma. Lahey, Gordon, and Segond forceps are all good options.

▸ Myotomes. Cobb and Langenbeck periosteal elevators that have been modified into both chisel tip and spoon tip myotomes can be helpful for enucleation.

With the proper equipment and surgical skills, vaginal hysterectomy is feasible in most cases, and the reduced morbidity, costs, and hospital length of stay associated with this approach should be enough incentive to encourage gynecologists to increase proficiency in the vaginal approach, Dr. Zimmerman said.

Keep in mind, he added, that in appropriately informed patients who have given consent to surgery, conversion to a more invasive approach is not a complication.

Dr. Zimmerman is a speaker/proctor for Cook Medical, proctor for Boston Scientific Corp. and Covidien, and receives Royalties from Lumitex Inc. and Marina Medical Instruments Inc.

ST. LOUIS — The vast majority of benign hysterectomies can – and should – be performed vaginally, according to Dr. Carl W. Zimmerman.

In fact, more than 90% of uteri weighing less than 250 g are accessible and can safely be removed vaginally by using guidelines endorsed by the board of directors of the Society of Pelvic Reconstructive Surgeons. Considerable evidence exists that many larger uteri also can be removed safely via the vaginal route, he said at the conference, which was sponsored by the society.

Despite this evidence, however, the minimally invasive vaginal approach remains underused in the United States, said Dr. Zimmerman, professor of obstetrics and gynecology at Vanderbilt University, Nashville, Tenn.

A lack of experience, familiarity with technique, and confidence is the main reasons why surgeons avoid the vaginal approach in favor of more invasive abdominal, laparoscopic, and robotic techniques. While the choice for vaginal hysterectomy should be made based – to a certain extent – on guidelines, it is important to consider skill acquisition, experience and competency, he said.

He encouraged those who are “on a learning curve” in terms of performing vaginal hysterectomy in patients with large uteri to obtain more experience by using this technique for uteri of 14–16 week size.

“That may sound big, but you'll be amazed, you'll be empowered, and your patients will do well,” he said, strongly recommending consideration of the concept of removing larger uteri by this method.

He outlined five main steps that must be completed to successfully remove an enlarged uterus vaginally, and provided tips on surgical instrumentation that can facilitate vaginal hysterectomy in cases involving a large uterus.

The first step is entry into the peritoneal cavity. This can be accomplished anteriorly or posteriorly, but experienced operators will delay entry into the anterior segment until the uterosacral and cardinal ligaments have been detached, and therefore they typically enter posteriorly.

“It's often available to you, and it's the easiest entry into the peritoneal cavity,” he said of the posterior approach.

The next two steps are to detach the uterosacral and cardinal ligaments, and to ligate the uterine artery.

Keep in mind that fibroids are the most common cause of uterine enlargement, and that most of the anatomical distortions in the fibroid uterus are limited to the area superior to the uterine artery. This “concept of uterine anatomic distortion” means that once steps 1–3 are completed, you “can be innovative about the way you debulk and remove the uterus. Once you have secured the support system, and you have divided the blood supply, then it becomes a mechanical exercise in converting a roughly globular structure into either various components that will come out, or a shape that will change and come out,” he explained.

Once the fourth step of debulking and removing the uterus is completed, the final step – vaginal adnexectomy – can be performed as needed based on the same indications that would be used if a scope was in place, or if the procedure was done abdominally, he said.

As for the best approaches to debulking the uterus, Dr. Zimmerman said morcellation is his primary technique, followed by coring, which is very useful for the adenomyotic uterus – and is particularly valuable for managing uteri up to 17 weeks in size.

The typical tools used in gynecologic surgery, such as Haney clamps, straight needle holders, and short instruments may be inadequate for performing vaginal hysterectomy involving large uteri. Instruments Dr. Zimmerman recommends for improving surgical skill and outcome include:

▸ Retractors. The correct retractors are one of the keys to success in vaginal hysterectomy; shop around and find the type that fits best into your system, Dr. Zimmerman advised. He listed Heaney, Harrington, malleable ribbon, Breisky-Navratil, and Steiner-Auvard among good options. Deaver retractors should be avoided because they increase risk of bladder injury, he said.

▸ Scissors. The right scissors can help with debulking when difficult angles are encountered. Jorgenson scissors, which Dr. Zimmerman learned to use in abdominal hysterectomy, are also useful in vaginal hysterectomy, because they create a right angle very valuable for debulking the uterus. Martin cartilage scissors, which have sharp points at the tips that can allow for insertion into a myoma and allow wedges to be cut, are very helpful, he said. Even a very dense or calcified myoma can be transected and debulked using these scissors.

▸ Lights. Whatever you choose to use to gain extra light is a good idea, he added. The Vital Vue surgical light, and a newer version – the Versalight, which is a multifunctional surgical light that provides irrigation, suction, and retraction, are good options. Dr. Zimmerman disclosed that he helped design the Versalight.

▸ Vulsellum forceps. These are useful for grasping myoma. Lahey, Gordon, and Segond forceps are all good options.

▸ Myotomes. Cobb and Langenbeck periosteal elevators that have been modified into both chisel tip and spoon tip myotomes can be helpful for enucleation.

With the proper equipment and surgical skills, vaginal hysterectomy is feasible in most cases, and the reduced morbidity, costs, and hospital length of stay associated with this approach should be enough incentive to encourage gynecologists to increase proficiency in the vaginal approach, Dr. Zimmerman said.

Keep in mind, he added, that in appropriately informed patients who have given consent to surgery, conversion to a more invasive approach is not a complication.

Dr. Zimmerman is a speaker/proctor for Cook Medical, proctor for Boston Scientific Corp. and Covidien, and receives Royalties from Lumitex Inc. and Marina Medical Instruments Inc.

Major Finding: The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with the controls (rates of 0.156 vs. 0.075, respectively).

Data Source: A genome-wide analysis of CNVs in 366 children with ADHD and 1,047 controls.

Disclosures: The study was funded primarily by Wellcome Trust. Additional funding was provided by Action Research, Baily Thomas Charitable Trust, UK Medical Research Council, and the European Union. Study authors stated that they had no conflicts to report.

Attention-deficit hyperactivity disorder is a neurodevelopmental disorder, rather than a purely social construct, according to British researchers who have found that a type of genetic variation associated with brain disorders such as schizophrenia and autism also occurs in excess in ADHD patients.

The findings, published online in The Lancet, provide the first direct evidence of a genetic basis for ADHD, Dr. Nigel Williams of Cardiff University, Wales, and his colleagues reported.

The investigators performed a genome-wide analysis of large, rare chromosomal deletions and duplications known as copy number variants (CNVs) in 366 children with ADHD and 1,047 controls.

The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with that in the controls — rates of 0.156 and 0.075, respectively, they found (Lancet 2010 Sept. 30 [doi:10.1016/S0140-6736(10)61109-9]).

The CNVs identified in this study are similar to those found in patients with schizophrenia and autism, and are significantly enriched for loci that have previously been implicated in those disorders, with particular overlap at a region on chromosome 16 that spans a number of genes, including one that affects brain development.

Furthermore, although the rate of CNVs was significantly higher in children with ADHD with and without intellectual disability, compared with the general population, the rate was particularly high in those with intellectual disability, defined as those with an IQ of less than 70 (rates of 0.424 and 0.075, respectively).

The findings are noteworthy because despite evidence that ADHD might be a genetic condition — for example, it has an estimated heritability of 76% — there has been a great deal of debate over whether it is a result of bad parenting or other external factors, coauthor Dr. Anita Thapar said during a press conference on the findings.

“ADHD can be stigmatizing … and finding this direct genetic link to ADHD should help clear this misunderstanding and address this issue of stigma,” said Dr. Thapar, professor of child and adolescent psychiatry at Cardiff University.

In addition to providing a window into the biology of the brain, the findings will also influence the way in which ADHD is classified and will improve communication between scientists and clinicians about “what we mean by ADHD,” she said.

“This will be the start of a much more scientific venture because our findings are going to help us unravel the biologic basis of ADHD, and that's going to be really important in turn in the further future to help us develop new and much more effective treatments for affected individuals.”

The subjects were recruited from community clinics and had met diagnostic criteria for ADHD or hyperkinetic disorder. They were aged 5-17 years (mean, 10.5 years), were of white U.K. origin, and had a mean IQ of 86. Controls were unrelated, ethnically matched children from the 1958 British Birth Cohort.

The findings have important clinical and research implications. “First, our results emphasize that further investigation of CNVs in ADHD is a priority for research into this disorder,” the investigators wrote.

Also, the finding that more than a third of ADHD children with intellectual disability carried a large, rare CNV — and the fact that none of these children had been assessed for this type of mutation by clinical services — suggest that routine referral to clinical geneticists and screening for such mutations could be helpful for children with ADHD who also have intellectual disability, they said.

View on the News

New Insights on Brain Development

The findings of this study provide “a new chapter to the genetics of neurodevelopmental disorders,” Dr. J. Peter H. Burbach said.

Not only do they give insight into the neurological basis of ADHD, they also show that ADHD shares specific genes with autism, schizophrenia, and mental retardation. In particular, they highlight the importance of the chromosome 16p13.11 region previously implicated in these and other brain disorders, he said.

However, although the findings are exciting, it remains unclear how they will be clinically translated, he said, noting that to help clinician's better understand and interpret the diversity of neuropsychiatric phenotypes in light of these findings about overlapping genotypes, future studies should explore in more detail how the genotypes and phenotypes are linked.

“The first gains beyond today's study might be initial insight into the pathogenesis and neurobiology of brain development as influenced by these genetic variants,” he wrote, adding, “This knowledge will eventually enter the clinic and might affect the way people think about and treat neurodevelopmental disorders by accounting for the biological consequence of the specific patient's genotype.”

DR. BURBACH is with the department of neuroscience and pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands. He wrote a commentary accompanying the report (Lancet 2010 Sept. 30 [doi: 10.1016/S0140-6736(10)61192-0)]. He reported having no conflicts of interest.

Major Finding: The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with the controls (rates of 0.156 vs. 0.075, respectively).

Data Source: A genome-wide analysis of CNVs in 366 children with ADHD and 1,047 controls.

Disclosures: The study was funded primarily by Wellcome Trust. Additional funding was provided by Action Research, Baily Thomas Charitable Trust, UK Medical Research Council, and the European Union. Study authors stated that they had no conflicts to report.

Attention-deficit hyperactivity disorder is a neurodevelopmental disorder, rather than a purely social construct, according to British researchers who have found that a type of genetic variation associated with brain disorders such as schizophrenia and autism also occurs in excess in ADHD patients.

The findings, published online in The Lancet, provide the first direct evidence of a genetic basis for ADHD, Dr. Nigel Williams of Cardiff University, Wales, and his colleagues reported.

The investigators performed a genome-wide analysis of large, rare chromosomal deletions and duplications known as copy number variants (CNVs) in 366 children with ADHD and 1,047 controls.

The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with that in the controls — rates of 0.156 and 0.075, respectively, they found (Lancet 2010 Sept. 30 [doi:10.1016/S0140-6736(10)61109-9]).

The CNVs identified in this study are similar to those found in patients with schizophrenia and autism, and are significantly enriched for loci that have previously been implicated in those disorders, with particular overlap at a region on chromosome 16 that spans a number of genes, including one that affects brain development.

Furthermore, although the rate of CNVs was significantly higher in children with ADHD with and without intellectual disability, compared with the general population, the rate was particularly high in those with intellectual disability, defined as those with an IQ of less than 70 (rates of 0.424 and 0.075, respectively).

The findings are noteworthy because despite evidence that ADHD might be a genetic condition — for example, it has an estimated heritability of 76% — there has been a great deal of debate over whether it is a result of bad parenting or other external factors, coauthor Dr. Anita Thapar said during a press conference on the findings.

“ADHD can be stigmatizing … and finding this direct genetic link to ADHD should help clear this misunderstanding and address this issue of stigma,” said Dr. Thapar, professor of child and adolescent psychiatry at Cardiff University.

In addition to providing a window into the biology of the brain, the findings will also influence the way in which ADHD is classified and will improve communication between scientists and clinicians about “what we mean by ADHD,” she said.

“This will be the start of a much more scientific venture because our findings are going to help us unravel the biologic basis of ADHD, and that's going to be really important in turn in the further future to help us develop new and much more effective treatments for affected individuals.”

The subjects were recruited from community clinics and had met diagnostic criteria for ADHD or hyperkinetic disorder. They were aged 5-17 years (mean, 10.5 years), were of white U.K. origin, and had a mean IQ of 86. Controls were unrelated, ethnically matched children from the 1958 British Birth Cohort.

The findings have important clinical and research implications. “First, our results emphasize that further investigation of CNVs in ADHD is a priority for research into this disorder,” the investigators wrote.

Also, the finding that more than a third of ADHD children with intellectual disability carried a large, rare CNV — and the fact that none of these children had been assessed for this type of mutation by clinical services — suggest that routine referral to clinical geneticists and screening for such mutations could be helpful for children with ADHD who also have intellectual disability, they said.

View on the News

New Insights on Brain Development

The findings of this study provide “a new chapter to the genetics of neurodevelopmental disorders,” Dr. J. Peter H. Burbach said.

Not only do they give insight into the neurological basis of ADHD, they also show that ADHD shares specific genes with autism, schizophrenia, and mental retardation. In particular, they highlight the importance of the chromosome 16p13.11 region previously implicated in these and other brain disorders, he said.

However, although the findings are exciting, it remains unclear how they will be clinically translated, he said, noting that to help clinician's better understand and interpret the diversity of neuropsychiatric phenotypes in light of these findings about overlapping genotypes, future studies should explore in more detail how the genotypes and phenotypes are linked.

“The first gains beyond today's study might be initial insight into the pathogenesis and neurobiology of brain development as influenced by these genetic variants,” he wrote, adding, “This knowledge will eventually enter the clinic and might affect the way people think about and treat neurodevelopmental disorders by accounting for the biological consequence of the specific patient's genotype.”

DR. BURBACH is with the department of neuroscience and pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands. He wrote a commentary accompanying the report (Lancet 2010 Sept. 30 [doi: 10.1016/S0140-6736(10)61192-0)]. He reported having no conflicts of interest.

Major Finding: The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with the controls (rates of 0.156 vs. 0.075, respectively).

Data Source: A genome-wide analysis of CNVs in 366 children with ADHD and 1,047 controls.

Disclosures: The study was funded primarily by Wellcome Trust. Additional funding was provided by Action Research, Baily Thomas Charitable Trust, UK Medical Research Council, and the European Union. Study authors stated that they had no conflicts to report.

Attention-deficit hyperactivity disorder is a neurodevelopmental disorder, rather than a purely social construct, according to British researchers who have found that a type of genetic variation associated with brain disorders such as schizophrenia and autism also occurs in excess in ADHD patients.

The findings, published online in The Lancet, provide the first direct evidence of a genetic basis for ADHD, Dr. Nigel Williams of Cardiff University, Wales, and his colleagues reported.

The investigators performed a genome-wide analysis of large, rare chromosomal deletions and duplications known as copy number variants (CNVs) in 366 children with ADHD and 1,047 controls.

The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with that in the controls — rates of 0.156 and 0.075, respectively, they found (Lancet 2010 Sept. 30 [doi:10.1016/S0140-6736(10)61109-9]).

The CNVs identified in this study are similar to those found in patients with schizophrenia and autism, and are significantly enriched for loci that have previously been implicated in those disorders, with particular overlap at a region on chromosome 16 that spans a number of genes, including one that affects brain development.

Furthermore, although the rate of CNVs was significantly higher in children with ADHD with and without intellectual disability, compared with the general population, the rate was particularly high in those with intellectual disability, defined as those with an IQ of less than 70 (rates of 0.424 and 0.075, respectively).

The findings are noteworthy because despite evidence that ADHD might be a genetic condition — for example, it has an estimated heritability of 76% — there has been a great deal of debate over whether it is a result of bad parenting or other external factors, coauthor Dr. Anita Thapar said during a press conference on the findings.

“ADHD can be stigmatizing … and finding this direct genetic link to ADHD should help clear this misunderstanding and address this issue of stigma,” said Dr. Thapar, professor of child and adolescent psychiatry at Cardiff University.

In addition to providing a window into the biology of the brain, the findings will also influence the way in which ADHD is classified and will improve communication between scientists and clinicians about “what we mean by ADHD,” she said.

“This will be the start of a much more scientific venture because our findings are going to help us unravel the biologic basis of ADHD, and that's going to be really important in turn in the further future to help us develop new and much more effective treatments for affected individuals.”

The subjects were recruited from community clinics and had met diagnostic criteria for ADHD or hyperkinetic disorder. They were aged 5-17 years (mean, 10.5 years), were of white U.K. origin, and had a mean IQ of 86. Controls were unrelated, ethnically matched children from the 1958 British Birth Cohort.

The findings have important clinical and research implications. “First, our results emphasize that further investigation of CNVs in ADHD is a priority for research into this disorder,” the investigators wrote.

Also, the finding that more than a third of ADHD children with intellectual disability carried a large, rare CNV — and the fact that none of these children had been assessed for this type of mutation by clinical services — suggest that routine referral to clinical geneticists and screening for such mutations could be helpful for children with ADHD who also have intellectual disability, they said.

View on the News

New Insights on Brain Development

The findings of this study provide “a new chapter to the genetics of neurodevelopmental disorders,” Dr. J. Peter H. Burbach said.

Not only do they give insight into the neurological basis of ADHD, they also show that ADHD shares specific genes with autism, schizophrenia, and mental retardation. In particular, they highlight the importance of the chromosome 16p13.11 region previously implicated in these and other brain disorders, he said.

However, although the findings are exciting, it remains unclear how they will be clinically translated, he said, noting that to help clinician's better understand and interpret the diversity of neuropsychiatric phenotypes in light of these findings about overlapping genotypes, future studies should explore in more detail how the genotypes and phenotypes are linked.

“The first gains beyond today's study might be initial insight into the pathogenesis and neurobiology of brain development as influenced by these genetic variants,” he wrote, adding, “This knowledge will eventually enter the clinic and might affect the way people think about and treat neurodevelopmental disorders by accounting for the biological consequence of the specific patient's genotype.”

DR. BURBACH is with the department of neuroscience and pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands. He wrote a commentary accompanying the report (Lancet 2010 Sept. 30 [doi: 10.1016/S0140-6736(10)61192-0)]. He reported having no conflicts of interest.

Major Finding: After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point).

Data Source: A prospective cohort study involving 187 patients from the DREAM registry.

Disclosures: The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough, Roche Pharmaceuticals, UCB Pharma, and Bristol-Myers Squibb.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point).

The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 9 months vs. 7 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All of the patients who participated in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion.

Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline.

The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar in demographic characteristics.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, noted the investigators, who added that lack of randomization was another limitation of little concern, because “confounding by indication is unlikely.”

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

“Significant interactions of statins with RTX in RA have not previously been shown.

“A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed,” according to Dr. Arts and co-investigators.

Major Finding: After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point).

Data Source: A prospective cohort study involving 187 patients from the DREAM registry.

Disclosures: The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough, Roche Pharmaceuticals, UCB Pharma, and Bristol-Myers Squibb.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point).

The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 9 months vs. 7 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All of the patients who participated in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion.

Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline.

The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar in demographic characteristics.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, noted the investigators, who added that lack of randomization was another limitation of little concern, because “confounding by indication is unlikely.”

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

“Significant interactions of statins with RTX in RA have not previously been shown.

“A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed,” according to Dr. Arts and co-investigators.

Major Finding: After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point).

Data Source: A prospective cohort study involving 187 patients from the DREAM registry.

Disclosures: The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough, Roche Pharmaceuticals, UCB Pharma, and Bristol-Myers Squibb.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point).

The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 9 months vs. 7 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All of the patients who participated in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion.

Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline.

The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar in demographic characteristics.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, noted the investigators, who added that lack of randomization was another limitation of little concern, because “confounding by indication is unlikely.”

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

“Significant interactions of statins with RTX in RA have not previously been shown.

“A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed,” according to Dr. Arts and co-investigators.

Major Finding: Compared with patients in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at 14 weeks' follow-up (−3.0 vs. 0.0 point change); the improvement was sustained at 24-week follow-up (−3.0 vs. −1.0 point change).

Data Source: A randomized, placebo-controlled study of 356 patients with ankylosing spondylitis.

Disclosures: This study was funded by Centocor Research and Development and the Schering-Plough Research Institute. Dr. Deodhar disclosed that he has received payments from, and served on the advisory board for Centocor. Other authors on the study disclosed receiving consultancy fees, speaking fees, and/or honoraria from numerous pharmaceutical companies.

The anti–tumor necrosis factor–alpha agent golimumab significantly reduced sleep disturbance and improved health-related quality of life in a randomized placebo-controlled trial of 356 patients with ankylosing spondylitis.

The investigators assessed sleep disturbance using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which asks patients how many times in the past month they have had trouble falling asleep, awakened several times per night, had trouble staying asleep (including waking far too early), and/or awakened after their usual amount of sleep feeling tired and worn out. On the scale, the possible answers for each question were 0 (not at all), 1 (1–3 days), 2 (4–7 days), 3 (8–14 days), 4 (15–21 days), and 5 (22–31 days). Thus, the total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance.

Study participants, who had moderate-to-severe sleep disturbance at baseline because of underlying pain associated with AS, were randomized to receive either placebo or treatment with 50 mg or 100 mg of golimumab subcutaneously every 4 weeks.

Most of the study participants were men. Their mean time since AS diagnosis was 11 years for the placebo group and 8 years for each golimumab group. The mean baseline JSEQ score was 10 for the placebo group, 10 for the 50-mg group, and 11 for the 100-mg group.

Compared with those in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at the 14-week follow-up (−3.0 vs. 0.0 point change), and the improvement was sustained at 24-week follow-up (−3.0 vs. −1.0 point change), Dr. Atul Deodhar, medical director of the rheumatology clinic at the Oregon Health & Science University, Portland, and colleagues reported.

The effect was similar with both the 50- and 100-mg golimumab dose, the investigators noted (Arthritis Care Res. 2010:62:1266–71).

The findings of this study − which is a secondary analysis of the previously reported GO-RAISE study that evaluated golimumab in AS patients – also showed that changes in the JSEQ scores during the course of the study significantly correlated with changes from baseline on Short Form–36 Health Survey summary scores, Bath AS Functional Index scores, Bath AS Disease Activity Index, inflammation assessments, and total and night back-pain scores.

Improvements in the night back-pain scores were the strongest predictor of improvement in sleep disturbance as measured by JSEQ scores.

Golimumab (Simponi) has Food and Drug Administration approval for treatment – with methotrexate – of moderately to severely active rheumatoid arthritis in adults; in the treatment of active psoriatic arthritis, in which it can be given with or without methotrexate; and in the treatment of active ankylosing spondylitis.

Major Finding: Compared with patients in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at 14 weeks' follow-up (−3.0 vs. 0.0 point change); the improvement was sustained at 24-week follow-up (−3.0 vs. −1.0 point change).

Data Source: A randomized, placebo-controlled study of 356 patients with ankylosing spondylitis.

Disclosures: This study was funded by Centocor Research and Development and the Schering-Plough Research Institute. Dr. Deodhar disclosed that he has received payments from, and served on the advisory board for Centocor. Other authors on the study disclosed receiving consultancy fees, speaking fees, and/or honoraria from numerous pharmaceutical companies.

The anti–tumor necrosis factor–alpha agent golimumab significantly reduced sleep disturbance and improved health-related quality of life in a randomized placebo-controlled trial of 356 patients with ankylosing spondylitis.

The investigators assessed sleep disturbance using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which asks patients how many times in the past month they have had trouble falling asleep, awakened several times per night, had trouble staying asleep (including waking far too early), and/or awakened after their usual amount of sleep feeling tired and worn out. On the scale, the possible answers for each question were 0 (not at all), 1 (1–3 days), 2 (4–7 days), 3 (8–14 days), 4 (15–21 days), and 5 (22–31 days). Thus, the total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance.

Study participants, who had moderate-to-severe sleep disturbance at baseline because of underlying pain associated with AS, were randomized to receive either placebo or treatment with 50 mg or 100 mg of golimumab subcutaneously every 4 weeks.

Most of the study participants were men. Their mean time since AS diagnosis was 11 years for the placebo group and 8 years for each golimumab group. The mean baseline JSEQ score was 10 for the placebo group, 10 for the 50-mg group, and 11 for the 100-mg group.

Compared with those in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at the 14-week follow-up (−3.0 vs. 0.0 point change), and the improvement was sustained at 24-week follow-up (−3.0 vs. −1.0 point change), Dr. Atul Deodhar, medical director of the rheumatology clinic at the Oregon Health & Science University, Portland, and colleagues reported.

The effect was similar with both the 50- and 100-mg golimumab dose, the investigators noted (Arthritis Care Res. 2010:62:1266–71).

The findings of this study − which is a secondary analysis of the previously reported GO-RAISE study that evaluated golimumab in AS patients – also showed that changes in the JSEQ scores during the course of the study significantly correlated with changes from baseline on Short Form–36 Health Survey summary scores, Bath AS Functional Index scores, Bath AS Disease Activity Index, inflammation assessments, and total and night back-pain scores.

Improvements in the night back-pain scores were the strongest predictor of improvement in sleep disturbance as measured by JSEQ scores.

Golimumab (Simponi) has Food and Drug Administration approval for treatment – with methotrexate – of moderately to severely active rheumatoid arthritis in adults; in the treatment of active psoriatic arthritis, in which it can be given with or without methotrexate; and in the treatment of active ankylosing spondylitis.

Major Finding: Compared with patients in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at 14 weeks' follow-up (−3.0 vs. 0.0 point change); the improvement was sustained at 24-week follow-up (−3.0 vs. −1.0 point change).

Data Source: A randomized, placebo-controlled study of 356 patients with ankylosing spondylitis.

Disclosures: This study was funded by Centocor Research and Development and the Schering-Plough Research Institute. Dr. Deodhar disclosed that he has received payments from, and served on the advisory board for Centocor. Other authors on the study disclosed receiving consultancy fees, speaking fees, and/or honoraria from numerous pharmaceutical companies.

The anti–tumor necrosis factor–alpha agent golimumab significantly reduced sleep disturbance and improved health-related quality of life in a randomized placebo-controlled trial of 356 patients with ankylosing spondylitis.

The investigators assessed sleep disturbance using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which asks patients how many times in the past month they have had trouble falling asleep, awakened several times per night, had trouble staying asleep (including waking far too early), and/or awakened after their usual amount of sleep feeling tired and worn out. On the scale, the possible answers for each question were 0 (not at all), 1 (1–3 days), 2 (4–7 days), 3 (8–14 days), 4 (15–21 days), and 5 (22–31 days). Thus, the total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance.

Study participants, who had moderate-to-severe sleep disturbance at baseline because of underlying pain associated with AS, were randomized to receive either placebo or treatment with 50 mg or 100 mg of golimumab subcutaneously every 4 weeks.

Most of the study participants were men. Their mean time since AS diagnosis was 11 years for the placebo group and 8 years for each golimumab group. The mean baseline JSEQ score was 10 for the placebo group, 10 for the 50-mg group, and 11 for the 100-mg group.

Compared with those in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at the 14-week follow-up (−3.0 vs. 0.0 point change), and the improvement was sustained at 24-week follow-up (−3.0 vs. −1.0 point change), Dr. Atul Deodhar, medical director of the rheumatology clinic at the Oregon Health & Science University, Portland, and colleagues reported.

The effect was similar with both the 50- and 100-mg golimumab dose, the investigators noted (Arthritis Care Res. 2010:62:1266–71).

The findings of this study − which is a secondary analysis of the previously reported GO-RAISE study that evaluated golimumab in AS patients – also showed that changes in the JSEQ scores during the course of the study significantly correlated with changes from baseline on Short Form–36 Health Survey summary scores, Bath AS Functional Index scores, Bath AS Disease Activity Index, inflammation assessments, and total and night back-pain scores.

Improvements in the night back-pain scores were the strongest predictor of improvement in sleep disturbance as measured by JSEQ scores.

Golimumab (Simponi) has Food and Drug Administration approval for treatment – with methotrexate – of moderately to severely active rheumatoid arthritis in adults; in the treatment of active psoriatic arthritis, in which it can be given with or without methotrexate; and in the treatment of active ankylosing spondylitis.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 31% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower in the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31% compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18-55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course … we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide, which was also reported at the ECTRIMS congress, showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study. Also, teriflunomide in combination with subcutaneous injection of interferon beta-1a has been shown to improve MRI outcomes in MS patients to a significantly greater extent than does interferon beta-1a and placebo.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 31% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower in the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31% compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18-55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course … we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide, which was also reported at the ECTRIMS congress, showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study. Also, teriflunomide in combination with subcutaneous injection of interferon beta-1a has been shown to improve MRI outcomes in MS patients to a significantly greater extent than does interferon beta-1a and placebo.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 31% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower in the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31% compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18-55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course … we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide, which was also reported at the ECTRIMS congress, showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study. Also, teriflunomide in combination with subcutaneous injection of interferon beta-1a has been shown to improve MRI outcomes in MS patients to a significantly greater extent than does interferon beta-1a and placebo.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31% compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis.

The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added.

The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred.

Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital said the results from a second phase III study of teriflunomide are expected to be reported in 2012. He and Dr. Comi are investigators in the TEMSO trial.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31% compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis.

The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added.

The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred.

Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital said the results from a second phase III study of teriflunomide are expected to be reported in 2012. He and Dr. Comi are investigators in the TEMSO trial.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31% compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O'Connor reported at the congress.

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis.

The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O'Connor of St. Michael's Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added.

The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred.

Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital said the results from a second phase III study of teriflunomide are expected to be reported in 2012. He and Dr. Comi are investigators in the TEMSO trial.